@article {1420, title = {A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study.}, journal = {AJNR Am J Neuroradiol}, volume = {15}, year = {1994}, month = {1994 Oct}, pages = {1625-33}, abstract = {

PURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history.

METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (< or = 3 mm) and large (> 3 mm) "infarctlike" lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9.

RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95\% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8 MR evidence of infarctlike lesions was present in 77\% of the participants with histories of stroke but was also present in 23\% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm.

CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke.

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebral Ventricles, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Diagnosis, Differential, Feasibility Studies, Female, Humans, Image Interpretation, Computer-Assisted, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mass Screening, Observer Variation, Pilot Projects, Prospective Studies, Risk Factors, United States}, issn = {0195-6108}, author = {Bryan, R N and Manolio, T A and Schertz, L D and Jungreis, C and Poirier, V C and Elster, A D and Kronmal, R A} } @article {1415, title = {Subclinical disease as an independent risk factor for cardiovascular disease.}, journal = {Circulation}, volume = {92}, year = {1995}, month = {1995 Aug 15}, pages = {720-6}, abstract = {

BACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study.

METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes.

CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Female, Humans, Incidence, Longitudinal Studies, Male, Myocardial Infarction, Odds Ratio, Reference Values, Risk Factors}, issn = {0009-7322}, author = {Kuller, L H and Shemanski, L and Psaty, B M and Borhani, N O and Gardin, J and Haan, M N and O{\textquoteright}Leary, D H and Savage, P J and Tell, G S and Tracy, R} } @article {1450, title = {Surveillance and ascertainment of cardiovascular events. The Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {5}, year = {1995}, month = {1995 Jul}, pages = {278-85}, abstract = {

While previous prospective multicenter studies have conducted cardiovascular disease surveillance, few have detailed the techniques relating to the ascertainment of and data collection for events. The Cardiovascular Health Study (CHS) is a population-based study of coronary heart disease and stroke in older adults. This article summarizes the CHS events protocol and describes the methods of surveillance and ascertainment of hospitalized and nonhospitalized events, the use of medical records and other support documents, organizational issues at the field center level, and the classification of events through an adjudication process. We present data on incidence and mortality, the classification of adjudicated events, and the agreement between classification by the Events Subcommittee and the medical records diagnostic codes. The CHS techniques are a successful model for complete ascertainment, investigation, and documentation of events in an older cohort.

}, keywords = {Aged, Cerebrovascular Disorders, Coronary Disease, Epidemiologic Methods, Female, Hospitalization, Humans, Incidence, Longitudinal Studies, Male, Population Surveillance, Quality Control, United States}, issn = {1047-2797}, author = {Ives, D G and Fitzpatrick, A L and Bild, D E and Psaty, B M and Kuller, L H and Crowley, P M and Cruise, R G and Theroux, S} } @article {1467, title = {Prevalence and correlates of snoring and observed apneas in 5,201 older adults.}, journal = {Sleep}, volume = {19}, year = {1996}, month = {1996 Sep}, pages = {531-8}, abstract = {

The objectives of this study were to describe the prevalence of snoring, observed apneas, and daytime sleepiness in older men and women, and to describe the relationships of these sleep disturbances to health status and cardiovascular diseases (CVD). A cross-sectional design was employed to study sleep problems, CVD, general health, psychosocial factors, and medication use. The subjects were participants in the Cardiovascular Health Study, which included 5,201 adults, aged 65 and older, who were recruited from a random sample of Medicare enrollees in four U.S. communities. Study measures employed were sleep questions, echocardiography, carotid ultrasound, resting electrocardiogram, cognitive function, cardiopulmonary symptoms and diseases, depression, independent activities of daily living (IADLs), and benzodiazepine use. Thirty-three percent of the men and 19\% of the women reported loud snoring, which was less frequent in those over age 75. Snoring was positively associated with younger age, marital status, and alcohol use in men, and obesity, diabetes, and arthritis in women. Snoring was not associated, however, with cardiovascular risk factors or clinical CVD in men or women. Observed apneas were reported much less frequently (13\% of men and 4\% women) than snoring, and they were associated with alcohol use, chronic bronchitis, and marital status in men. Observed apneas were associated with depression and diabetes in women. In both men and women, daytime sleepiness was associated with poor health, advanced age, and IADL limitations. The conclusions of the study were that loud snoring, observed apneas, and daytime sleepiness are not associated cross-sectionally with hypertension or prevalent CVD in elderly persons.

}, keywords = {Activities of Daily Living, Age Factors, Aged, Cardiovascular Diseases, Comorbidity, Female, Humans, Incidence, Lung Diseases, Male, Narcolepsy, Prevalence, Random Allocation, Sex Factors, Sleep Apnea Syndromes, Snoring}, issn = {0161-8105}, author = {Enright, P L and Newman, A B and Wahl, P W and Manolio, T A and Haponik, E F and Boyle, P J} } @article {1463, title = {Short-term predictors of incident stroke in older adults. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {27}, year = {1996}, month = {1996 Sep}, pages = {1479-86}, abstract = {

BACKGROUND AND PURPOSE: Risk factors for incident stroke have been examined in middle-aged persons, but less is known about stroke precursors in the elderly, who suffer the highest rates of stroke. Short-term risk factors for incident stroke were examined in a longitudinal, population-based study including extensive measures of subclinical disease.

METHODS: Prospective study of 5201 women and men aged 65 years and older was undertaken in the multicenter Cardiovascular Health Study.

RESULTS: During an average 3.31-year follow-up, 188 incident strokes occurred. Stroke incidence increased significantly with age and was similar in women and men. Factors associated with increased stroke risk in multivariate analysis included age, aspirin use, diabetes, impaired glucose tolerance, higher systolic blood pressure, increased time needed to walk 15 ft. frequent falls, elevated creatinine level, abnormal left ventricular (LV) wall motion and increased LV mass on echocardiography, ultrasound-defined carotid stenosis, and atrial fibrillation. Increased LV mass and carotid stenosis were associated with twofold and threefold increases in incidences of stroke, respectively (P < .001). Aspirin users had a 52\% higher risk of stroke (relative risk, 1.52; 95\% confidence interval, 1.1 to 2.0; P < .007) after adjustment for other factors. This association was present only among aspirin users without prior coronary disease, atrial fibrillation, claudication, or transient ischemic attack, who had an 84\% higher risk (relative risk, 1.84; 95\% confidence interval, 1.2 to 2.8).

CONCLUSIONS: Short-term risk of stroke has a complex relationship with aspirin use and is strongly related to subclinical disease in this sample of older adults. These relationships should be considered in assessing stroke risk in the elderly, in whom recognized and subclinical cardiovascular disease is highly prevalent.

}, keywords = {Age Factors, Aged, Cardiovascular Physiological Phenomena, Cerebrovascular Disorders, Cohort Studies, Female, Health Status, Humans, Incidence, Longitudinal Studies, Male, Multivariate Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, Time Factors}, issn = {0039-2499}, author = {Manolio, T A and Kronmal, R A and Burke, G L and O{\textquoteright}Leary, D H and Price, T R} } @article {1488, title = {Incidence of and risk factors for atrial fibrillation in older adults.}, journal = {Circulation}, volume = {96}, year = {1997}, month = {1997 Oct 07}, pages = {2455-61}, abstract = {

BACKGROUND: This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up.

METHODS AND RESULTS: In this cohort study, 5201 adults > or = 65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF.

CONCLUSIONS: The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.

}, keywords = {Adult, Aged, Atrial Fibrillation, Blood Glucose, Blood Pressure, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Electrocardiography, Female, Follow-Up Studies, Hospital Records, Humans, Incidence, Male, Prospective Studies, Risk Factors, United States}, issn = {0009-7322}, author = {Psaty, B M and Manolio, T A and Kuller, L H and Kronmal, R A and Cushman, M and Fried, L P and White, R and Furberg, C D and Rautaharju, P M} } @article {1504, title = {Aspirin use and incident stroke in the cardiovascular health study. CHS Collaborative Research Group.}, journal = {Stroke}, volume = {29}, year = {1998}, month = {1998 May}, pages = {887-94}, abstract = {

BACKGROUND AND PURPOSE: Randomized clinical trials testing aspirin in relatively low-risk, middle-aged people have consistently shown small increases in stroke associated with aspirin use. We analyzed the relationship between the regular use of aspirin and incident ischemic and hemorrhagic stroke among people aged 65 years or older participating in the Cardiovascular Health Study.

METHODS: We conducted a multivariate analysis of incident stroke rates in a prospectively assessed, observational cohort of 5011 elderly people followed for a mean of 4.2 years.

RESULTS: Participants had a mean age of 72 years, and 58\% were women. Twenty-three percent used aspirin frequently, and 17\% used aspirin infrequently at study entry. Frequent aspirin use was associated with an increased rate of ischemic stroke compared with nonusers (relative risk= 1.6; 95\% confidence interval [CI], 1.2 to 2.2; P=0.001). After adjustment for other stroke risk factors, women who used aspirin frequently or infrequently at study entry had a 1.8-fold (95\% CI, 1.2 to 2.8) and 1.6-fold (95\% CI, 0.9 to 3.0) increased risk of ischemic stroke, respectively (P<0.01, test for trend), compared with nonusers. In men, aspirin use was not statistically significantly associated with stroke risk. Findings were similar when aspirin use in the years before the incident stroke was used in the modeling. Aspirin use at entry was also associated with a 4-fold (95\% CI, 1.6 to 10.0) increase in risk of hemorrhagic stroke for both infrequent and frequent users of aspirin (P=0.003).

CONCLUSIONS: Aspirin use was associated with increased risks of ischemic stroke in women and hemorrhagic stroke overall in this elderly cohort, after adjustment for other stroke predictors. The possibility exists of confounding by reasons for aspirin use rather than cause and effect. Whether regular aspirin use increases stroke risk for elderly people without cardiovascular disease can only be determined by randomized clinical trials.

}, keywords = {Aged, Aspirin, Brain Ischemia, Cardiovascular Diseases, Cerebral Hemorrhage, Cerebrovascular Disorders, Cohort Studies, Cyclooxygenase Inhibitors, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Humans, Incidence, Male, Regression Analysis, Risk Factors, Sex Factors, Time Factors}, issn = {0039-2499}, author = {Kronmal, R A and Hart, R G and Manolio, T A and Talbert, R L and Beauchamp, N J and Newman, A} } @article {1520, title = {Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group.}, journal = {N Engl J Med}, volume = {340}, year = {1999}, month = {1999 Jan 07}, pages = {14-22}, abstract = {

BACKGROUND: The combined thickness of the intima and media of the carotid artery is associated with the prevalence of cardiovascular disease. We studied the associations between the thickness of the carotid-artery intima and media and the incidence of new myocardial infarction or stroke in persons without clinical cardiovascular disease.

METHODS: Noninvasive measurements of the intima and media of the common and internal carotid artery were made with high-resolution ultrasonography in 5858 subjects 65 years of age or older. Cardiovascular events (new myocardial infarction or stroke) served as outcome variables in subjects without clinical cardiovascular disease (4476 subjects) over a median follow-up period of 6.2 years.

RESULTS: The incidence of cardiovascular events correlated with measurements of carotid-artery intima-media thickness. The relative risk of myocardial infarction or stroke increased with intima-media thickness (P<0.001). The relative risk of myocardial infarction or stroke (adjusted for age and sex) for the quintile with the highest thickness as compared with the lowest quintile was 3.87 (95 percent confidence interval, 2.72 to 5.51). The association between cardiovascular events and intima-media thickness remained significant after adjustment for traditional risk factors, showing increasing risks for each quintile of combined intima-media thickness, from the second quintile (relative risk, 1.54; 95 percent confidence interval, 1.04 to 2.28), to the third (relative risk, 1.84; 95 percent confidence interval, 1.26 to 2.67), fourth (relative risk, 2.01; 95 percent confidence interval, 1.38 to 2.91), and fifth (relative risk, 3.15; 95 percent confidence interval, 2.19 to 4.52). The results of separate analyses of myocardial infarction and stroke paralleled those for the combined end point.

CONCLUSIONS: Increases in the thickness of the intima and media of the carotid artery, as measured noninvasively by ultrasonography, are directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of cardiovascular disease.

}, keywords = {Aged, Carotid Arteries, Cerebrovascular Disorders, Disease-Free Survival, Female, Humans, Incidence, Male, Myocardial Infarction, Proportional Hazards Models, Prospective Studies, Risk Factors, Tunica Intima, Tunica Media, Ultrasonography}, issn = {0028-4793}, doi = {10.1056/NEJM199901073400103}, author = {O{\textquoteright}Leary, D H and Polak, J F and Kronmal, R A and Manolio, T A and Burke, G L and Wolfson, S K} } @article {594, title = {Increased blood glucose and insulin, body size, and incident colorectal cancer.}, journal = {J Natl Cancer Inst}, volume = {91}, year = {1999}, month = {1999 Jul 07}, pages = {1147-54}, abstract = {

BACKGROUND: Abdominal obesity--an elevated level of visceral adipose tissue--has been linked to colorectal cancer. Furthermore, elevated levels of visceral adipose tissue have been associated with hyperinsulinemia, and insulin is a growth factor in the colon. We assessed whether waist circumference, a surrogate measure of visceral adipose tissue, and metabolic parameters associated with visceral adipose tissue were related to colorectal cancer.

METHODS: In the Cardiovascular Health Study cohort, we examined the relationship of baseline measurements of body size, glucose, insulin, and lipoproteins to incident colorectal cancer. All P values are two-sided.

RESULTS: Among 5849 participants, 102 incident cases of colorectal cancer were identified. Individuals in the highest quartile of fasting glucose had a nearly twofold increased risk of colorectal cancer (relative risk [RR] = 1.8; 95\% confidence interval [CI] = 1.0-3.1), and the linear trend RR (LT RR = 1.2; 95\% CI = 1.0-1.5) for fasting glucose level was statistically significant (P =. 02). Glucose and insulin levels 2 hours after oral glucose challenge also exhibited statistically significant associations with colorectal cancer (2-hour glucose levels: RR = 2.4 [95\% CI = 1.2-4. 7]/LT RR = 1.3 [95\% CI = 1.0-1.6; P =.02]; 2-hour insulin levels: RR = 2.0 [95\% CI = 1.0-3.8]/LT RR = 1.2 [95\% CI = 1.0-1.5; P =.04]). Analysis of fasting insulin levels suggested a threshold effect, with values above the median associated with colorectal cancer (RR = 1.6; 95\% CI = 1.1-2.4; P =.02). Higher levels of waist circumference were also statistically significantly associated with colorectal cancer (RR = 1.9; 95\% CI = 1.1-3.3; P =.02).

CONCLUSIONS: These data provide, to our knowledge, the first direct evidence of an association between elevated visceral adipose tissue level, its associated metabolic effects, and colorectal cancer.

}, keywords = {Adipose Tissue, Aged, Blood Glucose, Body Constitution, Cholesterol, HDL, Colorectal Neoplasms, Female, Humans, Incidence, Insulin, Male, Prospective Studies, Risk, Triglycerides, Viscera}, issn = {0027-8874}, doi = {10.1093/jnci/91.13.1147}, author = {Schoen, R E and Tangen, C M and Kuller, L H and Burke, G L and Cushman, M and Tracy, R P and Dobs, A and Savage, P J} } @article {599, title = {Temporal trends in the use of anticoagulants among older adults with atrial fibrillation.}, journal = {Arch Intern Med}, volume = {159}, year = {1999}, month = {1999 Jul 26}, pages = {1574-8}, abstract = {

BACKGROUND: Several recent randomized clinical trials have demonstrated that warfarin sodium treatment, and to a lesser extent aspirin, reduces risk of stroke and death compared with placebo in persons with atrial fibrillation. Insufficient documentation exists on the extent to which the use of these therapies following trial publications has continued to increase in the elderly with atrial fibrillation.

METHODS: We used data from the Cardiovascular Health Study, a study of 5888 community-dwelling adults aged 65 years or older, to determine the prevalence of warfarin and aspirin use in persons with electrocardiogram-identified atrial fibrillation. Electrocardiogram examinations were conducted at baseline from 1989 through 1990, and at 6 subsequent annual examinations through 1995-1996. Medication data were collected by inventory methods at each examination. Temporal change in use of anticoagulants was analyzed by comparing percentage use in 1990 to use in each year through 1996.

RESULTS: The use of warfarin increased 4-fold from 13\% in 1990 to 50\% in 1996 among participants with prevalent atrial fibrillation (P<.001). Daily use of aspirin did not increase over time. Participants younger than 80 years were 4 times more likely to use warfarin in 1996 (P<.001) than those 80 years and older. Use of aspirin did not vary significantly with age.

CONCLUSIONS: Warfarin use in community-dwelling elderly persons with electrocardiogram-documented atrial fibrillation increased steadily following the first publication of its treatment benefit, reaching 50\% by 1996. In contrast, use of aspirin was unchanged during this same period. Continued efforts to promote appropriate anticoagulation therapy to physicians and their patients may still be needed.

}, keywords = {Aged, Anticoagulants, Aspirin, Atrial Fibrillation, Cerebrovascular Disorders, Drug Therapy, Electrocardiography, Female, Humans, Incidence, Male, Prevalence, Treatment Outcome, Warfarin}, issn = {0003-9926}, doi = {10.1001/archinte.159.14.1574}, author = {Smith, N L and Psaty, B M and Furberg, C D and White, R and Lima, J A and Newman, A B and Manolio, T A} } @article {593, title = {Traditional risk factors and subclinical disease measures as predictors of first myocardial infarction in older adults: the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {159}, year = {1999}, month = {1999 Jun 28}, pages = {1339-47}, abstract = {

BACKGROUND: Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease.

METHODS: In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model.

RESULTS: At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women.

CONCLUSIONS: After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.

}, keywords = {Age Distribution, Aged, Female, Follow-Up Studies, Humans, Incidence, Male, Multivariate Analysis, Myocardial Infarction, Predictive Value of Tests, Proportional Hazards Models, Risk, Risk Factors, Sex Distribution}, issn = {0003-9926}, doi = {10.1001/archinte.159.12.1339}, author = {Psaty, B M and Furberg, C D and Kuller, L H and Bild, D E and Rautaharju, P M and Polak, J F and Bovill, E and Gottdiener, J S} } @article {610, title = {Daytime sleepiness predicts mortality and cardiovascular disease in older adults. The Cardiovascular Health Study Research Group.}, journal = {J Am Geriatr Soc}, volume = {48}, year = {2000}, month = {2000 Feb}, pages = {115-23}, abstract = {

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD.

SETTING: Participants (n = 5888) were recruited in 1989, with an additional minority cohort recruited in 1993, in four US communities for a cohort study designed to evaluate risk factors for cardiovascular disease.

METHODS: An interview-administered questionnaire regarding health and sleep habits with ongoing ascertainment of total mortality and cardiovascular disease morbidity and mortality, including total CVD morbidity and mortality, incident myocardial infarction, and congestive heart failure.

RESULTS: Daytime sleepiness was the only sleep symptom that was significantly associated with mortality in both men and women. The unadjusted hazard ratio was 2.12 (1.66, 2.72) in women and 1.40 (1.12, 1.73) in men. Men who reported difficulty falling asleep also had an increased mortality rate (HR = 1.43 (1.14, 1.80)) which was not seen in women. The risks were attenuated with adjustment for age but remained significant for daytime sleepiness in women (HR = 1.82 (1.42, 2.34)) and for difficulty falling asleep in men. (HR = 1.29 (1.03, 1.63)). Frequent awakenings, early morning awakening, and snoring were not associated with a significantly increased risk of mortality in these older men and women. Crude event rates were evaluated for total incident cardiovascular morbidity and mortality, incident myocardial infarction, and incident congestive heart failure (CHF). Incident CVD rates were higher in both men and women with daytime sleepiness. The aged adjusted HR was 1.35 (95\% CI = 1.03, 1.76) in men and was 1.66 (95\% CI = 1.28, 2.16) in women. Incident CVD was not higher in those with any other sleep disturbance including snoring. The risk of CVD events associated with daytime sleepiness was attenuated but remained significant in women after adjustment for age. Incident myocardial infarction (MI) rates were also higher in women with daytime sleepiness but were not significantly higher in men. Incident CHF rates were increased in both men and women with daytime sleepiness. In men, the age adjusted HR was 1.49 (95\% CI, 1.12- 1.98) and in women, was 2.21 (95\% CI, 1.64-2.98). Women reporting both daytime sleepiness and frequent awakening had a hazard ratio of 2.34 (95\% CI, 1.66-3.29) for incident CHF compared with those with daytime sleepiness but without frequent awakening. This interaction was not found in men.

CONCLUSIONS: In this study, daytime sleepiness was the only sleep disturbance symptom that was associated with mortality, incident CVD morbidity and mortality, MI, and CHF. These findings were stronger in women than men, i.e., the associations persisted for mortality, CVD, and CHF in women after adjustment for age and other factors. Thus, a report of daytime sleepiness identifies older adults at increased risk for total and cardiovascular mortality, and is an independent risk factor in women.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Cardiovascular Diseases, Cohort Studies, Female, Health Status, Heart Failure, Humans, Incidence, Male, Multivariate Analysis, Myocardial Infarction, Odds Ratio, Risk Factors, Sex Factors, Sleep Apnea Syndromes, Sleep Stages, Sleep Wake Disorders, Snoring, Surveys and Questionnaires, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2000.tb03901.x}, author = {Newman, A B and Spiekerman, C F and Enright, P and Lefkowitz, D and Manolio, T and Reynolds, C F and Robbins, J} } @article {611, title = {Diabetes mellitus: subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {20}, year = {2000}, month = {2000 Mar}, pages = {823-9}, abstract = {

Previously diagnosed diabetes mellitus, newly diagnosed diabetes mellitus, and impaired glucose tolerance are important determinants of the risk of clinical cardiovascular disease (CVD). We have evaluated the relation of patients with subclinical CVD, diabetes, and impaired glucose tolerance and "normal" subjects and the risk of clinical CVD in the Cardiovascular Health Study. Diabetes (1343), impaired glucose tolerance (1433), and normal (2421) were defined by World Health Organization criteria at baseline in 1989 to 1990. The average follow-up was 6.4 years (mean age 73 years). Diabetics had a higher prevalence of clinical and subclinical CVD at baseline. Compared with diabetes in the absence of subclinical disease, the presence of subclinical CVD and diabetes was associated with significant increased adjusted relative risk of death (1.5, CI 0.93 to 2.41), relative risk of incident coronary heart disease (1.99, CI 1.25 to 3.19), and incident myocardial infarction (1.93, CI 0.96 to 3.91). The risk of clinical events was greater for participants with a history of diabetes compared with newly diagnosed diabetics at baseline. Compared with nondiabetic nonhypertensive subjects without subclinical disease, patients with a combination of diabetes, hypertension, and subclinical disease had a 12-fold increased risk of stroke. Fasting blood glucose levels were a weak predictor of incident coronary heart disease as were most other risk factors. Subclinical CVD was the primary determinant of clinical CVD among diabetics in the Cardiovascular Health Study.

}, keywords = {Aged, Arteriosclerosis, Coronary Disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Female, Humans, Incidence, Male, Multivariate Analysis, Myocardial Infarction, Prevalence, Proportional Hazards Models, Risk Factors, Sex Distribution, Stroke}, issn = {1079-5642}, doi = {10.1161/01.atv.20.3.823}, author = {Kuller, L H and Velentgas, P and Barzilay, J and Beauchamp, N J and O{\textquoteright}Leary, D H and Savage, P J} } @article {630, title = {Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study.}, journal = {Ann Intern Med}, volume = {134}, year = {2001}, month = {2001 Feb 06}, pages = {182-90}, abstract = {

BACKGROUND: Persons with abdominal aortic aneurysm are more likely to have a higher prevalence of risk factors for and clinical manifestations of cardiovascular disease. It is unknown whether these factors explain the high mortality rate associated with abdominal aortic aneurysm.

OBJECTIVE: To describe the risk for mortality, cardiovascular mortality, and cardiovascular morbidity in persons screened for abdominal aortic aneurysm.

DESIGN: Longitudinal cohort study.

SETTING: Four communities in the United States.

PARTICIPANTS: 4734 men and women older than 65 years of age recruited from Medicare eligibility lists.

MEASUREMENTS: Abdominal ultrasonography was used to measure the aortic diameter and the ratio of infrarenal to suprarenal measurement of aortic diameter in 1992-1993. Abdominal aortic aneurysm was defined as aortic diameter of 3 cm or greater or infrarenal-to-suprarenal ratio of 1.2 or greater. Mortality, cardiovascular disease mortality, incident cardiovascular disease, and repair or rupture were assessed after 4.5 years.

RESULTS: The prevalence of aneurysm was 8.8\%, and 87.7\% of aneurysms were 3.5 cm or less in diameter. Rates of total mortality (65.1 vs. 32.8 per 1000 person-years), cardiovascular mortality (34.3 vs. 13.8 per 1000 person-years), and incident cardiovascular disease (47.3 vs. 31.0 per 1000 person-years) were higher in participants with aneurysm than in those without aneurysm; after adjustment for age, risk factors, and presence of other cardiovascular disease, the respective relative risks were 1.32, 1.36, and 1.57. Rates of repair and rupture were low.

CONCLUSIONS: Rates of total mortality, cardiovascular disease mortality, and incident cardiovascular disease were higher in participants with abdominal aortic aneurysm than in those without aneurysm, independent of age, sex, other clinical cardiovascular disease, and extent of atherosclerosis detected by noninvasive testing. Persons with smaller aneurysms detected by ultrasonography should be advised to modify risk factors for cardiovascular disease while under surveillance for increase in the size of the aneurysm.

}, keywords = {Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal, Aortic Rupture, Cardiovascular Diseases, Disease Progression, Female, Humans, Incidence, Longitudinal Studies, Male, Mortality, Proportional Hazards Models, Risk Factors, Ultrasonography, United States}, issn = {0003-4819}, doi = {10.7326/0003-4819-134-3-200102060-00008}, author = {Newman, A B and Arnold, A M and Burke, G L and O{\textquoteright}Leary, D H and Manolio, T A} } @article {646, title = {Factors associated with healthy aging: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Mar}, pages = {254-62}, abstract = {

OBJECTIVES: To identify factors associated with remaining healthy in older adults.

DESIGN: Longitudinal cohort study.

SETTING: Data were collected at the four Cardiovascular Health Study field centers.

PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study.

MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes.

RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults.

CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.

}, keywords = {Aged, Aged, 80 and over, Aging, Cardiovascular Diseases, Cohort Studies, Diet, Exercise, Female, Health Status, Humans, Incidence, Life Style, Longitudinal Studies, Lung Diseases, Obstructive, Male, Neoplasms, Probability, Reference Values, Risk Factors, Sex Distribution, Socioeconomic Factors, Survival Rate, United States}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.4930254.x}, author = {Burke, G L and Arnold, A M and Bild, D E and Cushman, M and Fried, L P and Newman, A and Nunn, C and Robbins, J} } @article {639, title = {Frailty in older adults: evidence for a phenotype.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {56}, year = {2001}, month = {2001 Mar}, pages = {M146-56}, abstract = {

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established.

METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality.

RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9\%; it increased with age and was greater in women than men. Four-year incidence was 7.2\%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline).

CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Disabled Persons, Fatigue, Female, Frail Elderly, Humans, Incidence, Male, Muscle Weakness, Phenotype, Prevalence, Sex Distribution, United States, Weight Loss}, issn = {1079-5006}, doi = {10.1093/gerona/56.3.m146}, author = {Fried, L P and Tangen, C M and Walston, J and Newman, A B and Hirsch, C and Gottdiener, J and Seeman, T and Tracy, R and Kop, W J and Burke, G and McBurnie, M A} } @article {666, title = {Hypertension, heart rate, use of antihypertensives, and incident prostate cancer.}, journal = {Ann Epidemiol}, volume = {11}, year = {2001}, month = {2001 Nov}, pages = {534-42}, abstract = {

PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth.

METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants.

RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95\% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95\% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk.

CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.

}, keywords = {Aged, Antihypertensive Agents, Cohort Studies, Heart Rate, Humans, Hypertension, Incidence, Male, Proportional Hazards Models, Prostatic Neoplasms, Risk, United States}, issn = {1047-2797}, doi = {10.1016/s1047-2797(01)00246-0}, author = {Fitzpatrick, A L and Daling, J R and Furberg, C D and Kronmal, R A and Weissfeld, J L} } @article {668, title = {Incidence and predictors of coronary heart disease among older African Americans--the Cardiovascular Health Study.}, journal = {J Natl Med Assoc}, volume = {93}, year = {2001}, month = {2001 Nov}, pages = {423-9}, abstract = {

Although coronary heart disease (CHD) is the leading cause of death and morbidity in older African Americans, relatively little is known about the incidence and predictors of CHD in this population. This study was undertaken to determine the incidence and predictors of CHD in African-American men and women aged 65 years and older. The participants in this study included a total of 924 African-American men and women aged 65 years of age and older who participated in the Cardiovascular Health Study (CHS). The overall CHD incidence was 26.6 per 1,000 person-years of risk. Rates were higher in men than women (35.3 vs. 21.6) and in those 75 years or older than in those less than 75 years (31.3 vs. 24.5). In multivariate analysis, factors associated with higher risk of incident disease were male gender [relative risk (RR) = 1.8, 95\% confidence interval (CI) = 1.1, 2.7], diabetes mellitus (RR = 1.9, 95\% CI = 1.2, 2.9), total cholesterol (RR for 40 mg/dL increment = 1.3, 95\% CI = 1.0, 1.5), and low (i.e., <0.9) ankle-arm index (RR = 2.1, 95\% CI = 1.3, 3.4) after adjusting for age. Within this cohort of older African Americans, male gender, diabetes mellitus, total cholesterol, and low ankle-arm index and were independently predictive of incident events. These results suggest that the ankle-arm index, a measure of advanced atherosclerosis, should be further evaluated for its efficacy in identifying older African Americans at risk for incident clinical events.

}, keywords = {Age Distribution, Aged, Black or African American, Coronary Disease, Female, Health Status, Humans, Incidence, Male, Predictive Value of Tests}, issn = {0027-9684}, author = {Jackson, S A and Burke, G L and Thach, C and Cushman, M and Ives, D and Powe, N and Manolio, T A} } @article {648, title = {M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {87}, year = {2001}, month = {2001 May 01}, pages = {1051-7}, abstract = {

Previous studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86\% vs 97\%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.

}, keywords = {Aged, Aged, 80 and over, Analysis of Variance, Coronary Disease, Echocardiography, Doppler, Female, Heart Failure, Humans, Incidence, Male, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke}, issn = {0002-9149}, doi = {10.1016/s0002-9149(01)01460-6}, author = {Gardin, J M and McClelland, R and Kitzman, D and Lima, J A and Bommer, W and Klopfenstein, H S and Wong, N D and Smith, V E and Gottdiener, J} } @article {635, title = {Risk factors for hospitalized gastrointestinal bleeding among older persons. Cardiovascular Health Study Investigators.}, journal = {J Am Geriatr Soc}, volume = {49}, year = {2001}, month = {2001 Feb}, pages = {126-33}, abstract = {

OBJECTIVES: We sought to estimate the incidence of hospitalization for upper and lower gastrointestinal bleeding among older persons and to identify independent risk factors.

DESIGN: Prospective cohort study.

SETTING: The Cardiovascular Health Study (CHS).

PARTICIPANTS: 5,888 noninstitutionalized men and women age 65 years or older in four U.S. communities enrolled in the CHS.

MEASUREMENTS: Gastrointestinal bleeding events during the period 1989 through 1998 were identified using hospital discharge diagnosis codes and confirmed by medical records review. Risk-factor information was collected in a standardized fashion at study baseline and annually during follow-up.

RESULTS: Among CHS participants (mean baseline age 73.3 years, 42\% male), the incidence of hospitalized gastrointestinal bleeding was 6.8/1,000 person-years. In multivariate analyses, advanced age, male sex, unmarried status, cardiovascular disease, difficulty with daily activities, use of multiple medications, and use of oral anticoagulants were independent risk factors. Compared with nonsmokers, subjects who smoked more than half a pack per day had a multivariate-adjusted hazard ratio (HR) of 2.14 (95\% confidence interval [CI] = 1.22-3.75) for upper gastrointestinal bleeding and a multivariate-adjusted HR of 0.21 (95\% CI = 0.03-1.54) for lower gastrointestinal bleeding. Aspirin users did not have an elevated risk of upper gastrointestinal bleeding (HR = 0.76, 95\% CI = 0.52-1.11), and users of other nonsteroidal anti-inflammatory drugs had a HR of 1.54 (95 \% CI = 0.99-2.36). Low ankle-arm systolic blood pressure index was associated with higher risk of gastrointestinal bleeding among subjects with clinical cardiovascular disease but not among those without clinical cardiovascular disease.

CONCLUSION: This study identifies risk factors for gastrointestinal bleeding, such as disability, that may be amenable to modification. The findings will help clinicians to identify older persons who are at high risk for gastrointestinal bleeding.

}, keywords = {Activities of Daily Living, Age Distribution, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Anticoagulants, Aspirin, Cardiovascular Diseases, Female, Gastrointestinal Hemorrhage, Hospitalization, Humans, Incidence, Male, Multivariate Analysis, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Smoking, United States}, issn = {0002-8614}, doi = {10.1046/j.1532-5415.2001.49032.x}, author = {Kaplan, R C and Heckbert, S R and Koepsell, T D and Furberg, C D and Polak, J F and Schoen, R E and Psaty, B M} } @article {663, title = {Silent MRI infarcts and the risk of future stroke: the cardiovascular health study.}, journal = {Neurology}, volume = {57}, year = {2001}, month = {2001 Oct 09}, pages = {1222-9}, abstract = {

BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly.

OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors.

METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts.

RESULTS: Approximately 28\% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes).

CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.

}, keywords = {Aged, Cerebral Infarction, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Risk Factors, Stroke}, issn = {0028-3878}, doi = {10.1212/wnl.57.7.1222}, author = {Bernick, C and Kuller, L and Dulberg, C and Longstreth, W T and Manolio, T and Beauchamp, N and Price, T} } @article {691, title = {Cardiovascular risk factors and venous thromboembolism incidence: the longitudinal investigation of thromboembolism etiology.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 May 27}, pages = {1182-9}, abstract = {

BACKGROUND: The association between traditional cardiovascular risk factors and risk of venous thromboembolism (VTE) has not been extensively examined in prospective studies.

METHODS: To determine whether atherosclerotic risk factors are also associated with increased incidence of VTE, we conducted a prospective study of 19 293 men and women without previous VTE in 6 US communities between 1987 and 1998.

RESULTS: There were 215 validated VTE events (1.45 per 1000 person-years) during a median of 8 years of follow-up. The age-adjusted hazard ratio was 1.4 (95\% confidence interval [CI], 1.1-1.9) for men vs women, 1.6 (95\% CI, 1.2-2.2) for blacks vs whites, and 1.7 (95\% CI, 1.5-2.0) per decade of age. Cigarette smoking, hypertension, dyslipidemia, physical inactivity, and alcohol consumption were not associated with risk of VTE. Age-, race-, and sex-adjusted hazard ratios for body mass index categories (calculated as the weight in kilograms divided by the height in meters squared) of less than 25, 25 to less than 30, 30 to less than 35, 35 to less than 40, and 40 or more were 1.0, 1.5, 2.2, 1.5, and 2.7, respectively (P<.001 for the trend). Diabetes was also associated with an increased risk of VTE (adjusted hazard ratio, 1.5 [95\% CI, 1.0-2.1]).

CONCLUSIONS: Our data showing no relationship of some arterial risk factors with VTE corroborate the view that the etiology of VTE differs from atherosclerotic cardiovascular disease. In addition, the findings suggest a hypothesis that avoidance of obesity and diabetes or vigilance in prophylaxis in patients with those conditions may prevent some venous thromboses.

}, keywords = {Aged, Arteriosclerosis, Female, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Pulmonary Embolism, Risk Factors, United States, Venous Thrombosis}, issn = {0003-9926}, doi = {10.1001/archinte.162.10.1182}, author = {Tsai, Albert W and Cushman, Mary and Rosamond, Wayne D and Heckbert, Susan R and Polak, Joseph F and Folsom, Aaron R} } @article {692, title = {Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study.}, journal = {Stroke}, volume = {33}, year = {2002}, month = {2002 Jun}, pages = {1636-44}, abstract = {

BACKGROUND AND PURPOSE: Previous studies have reported an association between cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study (CHS) provides an opportunity to examine the relationship between vascular brain pathology seen on neuroimaging and changes in depressive symptoms.

METHODS: The sample included 3236 CHS participants who had an MRI brain scan. Demographic variables, medical history, functional status, and apolipoprotein E genotype were obtained at baseline. Annual scores on a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to 7 years subsequently.

RESULTS: After controlling for important covariates, occurrence of depressive symptoms (defined as modified CES-D score of >7) was associated with small lesions in the basal ganglia, large cortical white-matter lesions, and severe subcortical white-matter grade. Neuroimaging variables did not predict incident depression among those who were nondepressive at the time of MRI. Persistence of depressive symptoms across 2 consecutive time points was associated with small basal ganglia lesions and large cerebral cortical white-matter lesions. Worsening of depression (increase in CES-D score of > or =5) was associated with subcortical white-matter lesions.

CONCLUSIONS: These findings suggest that cerebrovascular disease at baseline is related to depression symptoms over time. Further studies are needed to investigate the differential effects of subcortical white- versus gray-matter lesions on mood.

}, keywords = {Aged, Aged, 80 and over, Basal Ganglia Cerebrovascular Disease, Brain, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Depression, Disease Progression, Female, Health Surveys, Humans, Incidence, Logistic Models, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Odds Ratio, United States}, issn = {1524-4628}, doi = {10.1161/01.str.0000018405.59799.d5}, author = {Steffens, David C and Krishnan, K Ranga Rama and Crump, Casey and Burke, Gregory L} } @article {703, title = {Incidence, manifestations, and predictors of brain infarcts defined by serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {33}, year = {2002}, month = {2002 Oct}, pages = {2376-82}, abstract = {

BACKGROUND AND PURPOSE: MRI-defined infarcts are common in the elderly. We sought to explore incidence, manifestations, and predictors of such infarcts.

METHODS: The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of 5888 people aged > or =65 years. Participants have had extensive baseline and follow-up evaluations; 1433 participants underwent 2 MRI scans separated by 5 years and had no infarcts on initial MRI.

RESULTS: On follow-up MRI, 254 participants (17.7\%) had 1 or more infarcts. Most were single (75.6\%), subcortical (79.9\%), and small (3 to 20 mm in 87.0\%). Only 11.4\% of those with infarcts experienced a documented transient ischemic attack or stroke between the scans. Although participants were similar at initial MRI, those with MRI-defined infarcts on follow-up experienced greater decline than those without infarcts on the Modified Mini-Mental State Examination and Digit-Symbol Substitution test (both P<0.01). Severity of white matter changes on initial MRI was the strongest predictor of incident infarcts. When it was excluded from stepwise multivariable models, predictors were serum creatinine, age, and ankle-arm index.

CONCLUSIONS: Incident MRI-defined infarcts commonly affect the elderly. Most are small, subcortical, and not associated with acute symptoms recognized as a transient ischemic attack or stroke. Nonetheless, they cannot be considered silent because of their association with subtle cognitive deficits. These covert infarcts are associated with white matter changes, which may share a common pathophysiology. Whether control of vascular risk factors, such as blood pressure, would reduce the risk of developing these infarcts and associated cognitive decline deserves further investigation.

}, keywords = {Aged, Brain Infarction, California, Cohort Studies, Creatinine, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Maryland, Multivariate Analysis, Neuropsychological Tests, North Carolina, Odds Ratio, Pennsylvania, Predictive Value of Tests, Risk Factors}, issn = {1524-4628}, doi = {10.1161/01.str.0000032241.58727.49}, author = {Longstreth, W T and Dulberg, Corinne and Manolio, Teri A and Lewis, Michael R and Beauchamp, Norman J and O{\textquoteright}Leary, Daniel and Carr, Jeff and Furberg, Curt D} } @article {710, title = {Prospective study of the G20210A polymorphism in the prothrombin gene, plasma prothrombin concentration, and incidence of venous thromboembolism.}, journal = {Am J Hematol}, volume = {71}, year = {2002}, month = {2002 Dec}, pages = {285-90}, abstract = {

Case-control studies have indicated increased risk of venous thrombosis associated with the prothrombin gene G20210A polymorphism and with elevated plasma prothrombin levels. We sought to confirm these results in a prospective population-based study of 21,690 persons. We measured G20210A and prothrombin antigen on pre-event blood samples of 302 participants who developed venous thromboembolism (VTE) and 626 participants who remained free of VTE. Approximately 4.0\% of cases and 2.4\% of controls carried the G20210A polymorphism, but only one of 137 African Americans did. The odds ratio in whites was 1.87 (95\% CI = 0.85, 4.11)--higher for those who reported a prior history of VTE (OR = 5.44) than those reporting no VTE history (OR = 1.41) and in those with idiopathic VTE (OR = 2.51) than those with secondary VTE (OR = 1.38). There was no association between venous thromboembolism and plasma prothrombin antigen level. We estimated that the G20210A polymorphism may account for approximately 2.5\% of venous thromboembolism events in United States whites.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Case-Control Studies, European Continental Ancestry Group, Genotype, Humans, Incidence, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Prospective Studies, Prothrombin, Recurrence, Research Design, Risk Factors, Thromboembolism, United States}, issn = {0361-8609}, doi = {10.1002/ajh.10229}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Heckbert, Susan R and Aleksic, Nena} } @article {684, title = {A prospective study of venous thromboembolism in relation to factor V Leiden and related factors.}, journal = {Blood}, volume = {99}, year = {2002}, month = {2002 Apr 15}, pages = {2720-5}, abstract = {

The aim of this study was to examine the occurrence of venous thromboembolism (VTE) in relation to factor V-related risk factors. Using a nested case-control design combining 2 population-based prospective studies, we measured factor V Leiden, HR2 haplotype, activated protein C (APC) resistance, and plasma factor V antigen in 335 participants who developed VTE during 8 years of follow-up and 688 controls. The overall odds ratio (OR) of VTE was 3.67 (95\% CI, 2.20-6.12) in participants carrying factor V Leiden compared with noncarriers. APC resistance measured after predilution with factor V-deficient plasma conferred an OR of 2.58 (95\% CI, 1.62-4.10). All 3 participants homozygous for the HR2 haplotype had a VTE, and the OR of VTE for homozygosity was estimated to be 5.5 (95\% CI, 2.45-12.5). Carriers of the HR2 haplotype otherwise were not at increased risk of VTE overall (OR = 1.05; 95\% CI, 0.64-1.72), but double heterozygotes for HR2 and factor V Leiden carried an OR of idiopathic VTE of 16.3 (95\% CI, 1.7-159) compared with noncarriers. Factor V antigen also was not associated with VTE overall, but for participants with the combination of high factor V antigen plus factor V Leiden the OR of idiopathic VTE was 11.5 (95\% CI, 4.2-31.4). In the general population, APC resistance and factor V Leiden were important VTE risk factors; homozygosity for the HR2 haplotype may be a risk factor but was rare; otherwise, HR2 haplotype and factor V antigen were not risk factors except in carriers of factor V Leiden.

}, keywords = {Activated Protein C Resistance, Aged, Cohort Studies, Continental Population Groups, Factor V, Genotype, Haplotypes, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Prospective Studies, Risk Factors, Thromboembolism, Venous Thrombosis}, issn = {0006-4971}, doi = {10.1182/blood.v99.8.2720}, author = {Folsom, Aaron R and Cushman, Mary and Tsai, Michael Y and Aleksic, Nena and Heckbert, Susan R and Boland, Lori L and Tsai, Albert W and Yanez, N David and Rosamond, Wayne D} } @article {693, title = {Protein C, antithrombin, and venous thromboembolism incidence: a prospective population-based study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {22}, year = {2002}, month = {2002 Jun 01}, pages = {1018-22}, abstract = {

Although deficiencies of protein C and antithrombin, 2 natural plasma anticoagulants, are known risk factors for venous thrombosis, population-based prospective incidence data on these associations are lacking. Venous thromboembolic events have been identified in adults in 2 longitudinal cohort studies, the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS). Incidence was examined in relation to prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic events that were not due to cancer in the ARIC Study. The age-adjusted incidence was elevated 3.36-fold (95\% CI 1.24 to 9.11) in the 1.1\% of subjects with protein C values <2.0 mg/L compared with subjects with higher values. In contrast, in the ARIC Study and the CHS, there was no association between low plasma antithrombin and venous thromboembolism. In conclusion, in this population-based study, a low protein C, but not antithrombin, level has been determined to be associated with an increased incidence of venous thromboembolism. Attributable risk estimates suggest that low protein C levels account for approximately 2.5\% of venous thromboembolic events in the ARIC population.

}, keywords = {Adult, Aged, Aged, 80 and over, Antithrombins, Arteriosclerosis, Cohort Studies, Humans, Incidence, Longitudinal Studies, Middle Aged, Odds Ratio, Population Surveillance, Prospective Studies, Protein C, Protein C Deficiency, Pulmonary Embolism, Thromboembolism, Venous Thrombosis}, issn = {1524-4636}, doi = {10.1161/01.atv.0000017470.08363.ab}, author = {Folsom, Aaron R and Aleksic, Nena and Wang, Lu and Cushman, Mary and Wu, Kenneth K and White, Richard H} } @article {676, title = {A stroke prediction score in the elderly: validation and Web-based application.}, journal = {J Clin Epidemiol}, volume = {55}, year = {2002}, month = {2002 Feb}, pages = {129-36}, abstract = {

The objective of this study was to construct a prediction model for predicting stroke in an elderly U.S. population, and to assess the accuracy in this population of other previously published prediction models. The subjects were participants in the Cardiovascular Health Study: 2,495 men and 3,393 women age 65 years and older at baseline, and followed for 6.3 years. Among 5,711 participants free of baseline stroke, 399 strokes occurred. Sex-specific prediction equations were constructed using study variables that were most importantly related to incident stroke: age, systolic blood pressure, diabetes, ECG diagnosis of atrial fibrillation or left ventricular hypertrophy, confirmed history of cardiovascular disease, diabetes, time to walk 15 ft, and serum creatinine. The prediction rule was implemented as a risk score and in a Web-based interactive Java applet. Overall, the model predicted 5-year stroke risks ranging from less than 1 to 59\%. The 20\% of subjects in the highest predicted risk group had a 5-year actual stroke incidence rate of 15\%, while the 20\% lowest risk group had a 1\% incidence. Risk scores from two other studies performed well in these study participants. Effective discrimination between low and high stroke risk in the elderly was possible in this cohort with data that are easy to obtain. Evaluation of the generalizability and clinical usefulness of this prediction model requires further research.

}, keywords = {Aged, Aged, 80 and over, Blood Pressure, Female, Follow-Up Studies, Humans, Incidence, Male, Models, Cardiovascular, Predictive Value of Tests, Risk Factors, ROC Curve, Stroke, United States}, issn = {0895-4356}, doi = {10.1016/s0895-4356(01)00434-6}, author = {Lumley, Thomas and Kronmal, Richard A and Cushman, Mary and Manolio, Teri A and Goldstein, Steven} } @article {695, title = {Therapy with hydroxymethylglutaryl coenzyme a reductase inhibitors (statins) and associated risk of incident cardiovascular events in older adults: evidence from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {162}, year = {2002}, month = {2002 Jun 24}, pages = {1395-400}, abstract = {

BACKGROUND: Recommendations to treat older adults with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) for the primary prevention of coronary heart disease events are supported by a single clinical trial restricted to adults 73 years or younger with low levels of high-density lipoprotein cholesterol.

METHODS: We investigated the association of statin use with incident cardiovascular disease and all-cause mortality during up to 7.3 years{\textquoteright} follow-up of 1250 women and 664 men from the Cardiovascular Health Study. Study participants were 65 years and older and free of cardiovascular disease at baseline. They received drug therapy to lower cholesterol levels at baseline or no treatment with a recommendation for therapy according to the National Cholesterol Education Program guidelines. Use of these drugs was assessed annually. We used proportional-hazards models to calculate hazard ratios (HRs) and 95\% confidence intervals (CIs), adjusted for confounding variables.

RESULTS: We found 382 incident cardiovascular events (159 myocardial infarctions, 159 strokes, and 64 deaths due to coronary heart disease) and 362 total deaths from June 1, 1989, to May 31, 1997. Compared with no use of drugs to lower cholesterol levels, statin use was associated with decreased risk of cardiovascular events (multivariate HR, 0.44; 95\% CI, 0.27-0.71) and all-cause mortality (HR, 0.56; 95\% CI, 0.36-0.88). Similar associations were observed among participants 74 years or older at baseline.

CONCLUSIONS: Use of statins was associated with decreased risk of incident cardiovascular events among elderly adults. These findings lend support to the National Cholesterol Education Program guidelines, which recommend therapy for the lowering of cholesterol levels for older adults with hypercholesterolemia.

}, keywords = {Aged, Cholesterol, LDL, Coronary Disease, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hypolipidemic Agents, Incidence, Male, Multivariate Analysis, Proportional Hazards Models, Risk Factors, United States}, issn = {0003-9926}, doi = {10.1001/archinte.162.12.1395}, author = {Lemaitre, Rozenn N and Psaty, Bruce M and Heckbert, Susan R and Kronmal, Richard A and Newman, Anne B and Burke, Gregory L} } @article {733, title = {Beta2-adrenergic receptor polymorphisms and risk of incident cardiovascular events in the elderly.}, journal = {Circulation}, volume = {107}, year = {2003}, month = {2003 Apr 22}, pages = {2021-4}, abstract = {

BACKGROUND: Genetic polymorphisms at codons 16 and 27 of the beta2-adrenergic receptor have been associated with altered response to sympathetic stimulation. We examined these polymorphisms in relation to cardiovascular event risk in the Cardiovascular Health Study.

METHODS AND RESULTS: A total of 808 black and 4441 white participants (mean age, 73 years) were genotyped for the Arg16Gly and Gln27Glu polymorphisms of the beta2-adrenergic receptor. There were 702 incident coronary events, 438 ischemic strokes, and 1136 combined cardiovascular events during 7 to 10 years of follow-up. Allele frequencies differed by race but not by age or hypertension status. Glu27 carriers had a lower risk of coronary events than Gln27 homozygotes (hazard ratio, 0.82; 95\% CI, 0.70 to 0.95), and there was a suggestion of decreased risk among Gly16 carriers compared with Arg16 homozygotes (hazard ratio, 0.88; 95\% CI, 0.72 to 1.07). There was no association of beta2-adrenergic receptor genotype with ischemic stroke or combined cardiovascular events.

CONCLUSIONS: The Glu27 allele of the beta2-adrenergic receptor was associated with a lower risk of incident coronary events in this elderly population.

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Brain Ischemia, Cardiovascular Diseases, Cohort Studies, Comorbidity, Coronary Disease, European Continental Ancestry Group, Follow-Up Studies, Gene Frequency, Humans, Incidence, Linkage Disequilibrium, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Risk Assessment, Stroke, United States}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000065231.07729.92}, author = {Heckbert, Susan R and Hindorff, Lucia A and Edwards, Karen L and Psaty, Bruce M and Lumley, Thomas and Siscovick, David S and Tang, Zhonghua and Durda, J Peter and Kronmal, Richard A and Tracy, Russell P} } @article {741, title = {C-reactive protein, carotid intima-media thickness, and incidence of ischemic stroke in the elderly: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {108}, year = {2003}, month = {2003 Jul 15}, pages = {166-70}, abstract = {

BACKGROUND: Increased carotid artery intima-media thickness (IMT) and elevated C-reactive protein (CRP) are both associated with the occurrence of stroke. We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT.

METHODS AND RESULTS: We studied 5417 participants aged 65 years or older without preexisting stroke or chronic atrial fibrillation who were participants in the Cardiovascular Health Study. The hazard ratio of incident ischemic stroke was estimated by Cox proportional hazards regression. During 10.2 years of follow-up, 469 incident ischemic strokes occurred. The adjusted hazard ratios for ischemic stroke in the 2nd to 4th quartiles of baseline CRP, relative to the 1st quartile, were 1.19 (95\% CI 0.92 to 1.53), 1.05 (95\% CI 0.81 to 1.37), and 1.60 (95\% CI 1.23 to 2.08), respectively. With additional adjustment for carotid IMT, there was little confounding. The association of CRP with stroke was significantly different depending on IMT (P<0.02), with no association of CRP with stroke among those in the lowest IMT tertile and a significant association among those with higher levels of IMT.

CONCLUSIONS: We conclude that elevated CRP is a risk factor for ischemic stroke, independent of atherosclerosis severity as measured by carotid IMT. The association of CRP with stroke is more apparent in the presence of a higher carotid IMT. CRP and carotid IMT may each be independent integrals in determining the risk of ischemic stroke.

}, keywords = {Aged, Brain Ischemia, C-Reactive Protein, California, Carotid Arteries, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Maryland, North Carolina, Odds Ratio, Pennsylvania, Proportional Hazards Models, Risk Assessment, Risk Factors, Stroke, Tunica Intima, Tunica Media, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000079160.07364.6A}, author = {Cao, Jie J and Thach, Chau and Manolio, Teri A and Psaty, Bruce M and Kuller, Lewis H and Chaves, Paulo H M and Polak, Joseph F and Sutton-Tyrrell, Kim and Herrington, David M and Price, Thomas R and Cushman, Mary} } @article {740, title = {Hormone replacement therapy and the risk of incident congestive heart failure: the Cardiovascular Health Study.}, journal = {J Womens Health (Larchmt)}, volume = {12}, year = {2003}, month = {2003 May}, pages = {341-50}, abstract = {

BACKGROUND: The development of congestive heart failure (CHF) in older persons is related to a variety of mechanisms. Hormone replacement therapy (HRT) affects several of the pathways that may be important in the development of CHF. We hypothesized that HRT would be associated with a decreased risk of incident CHF.

METHODS: Using Cox proportional-hazards regression, we assessed the risk of incident CHF (n = 304) associated with time-dependent past and current use of HRT compared to never use. The Cardiovascular Health Study is a prospective cohort study of community-dwelling adults aged 65 years and older. This analysis included female participants without a history of CHF at baseline (n = 3223).

RESULTS: At baseline, 62\% were never users, 26\% were past users, and 12\% were current users of HRT. Compared with never users, the multivariable relative risk (RR) of CHF was 1.01 (95\% confidence interval [95\% CI] 0.76,1.34) for past users and 1.34 (0.93,1.94) for current users. Results were similar among most treatment and clinical subgroups, except that the association of current HRT with CHF appeared to depend on body mass index (BMI) or osteoporosis status. The RR was 0.82 (0.43,1.60) for normal weight women, 1.65 (0.95,2.88) for overweight women, and 2.22 (1.06,4.67) for obese women (p = 0.01 for interaction). Similarly, the RR was 0.15 (0.04,0.65) for women with osteoporosis and 1.82 (1.25,2.65) for women without osteoporosis (p = 0.001 for interaction).

CONCLUSIONS: Overall, HRT was not associated with the risk of incident CHF, although BMI and osteoporosis appeared to modify the association of HRT with CHF. The risk of CHF was lower in patients with lower BMI or osteoporosis.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cohort Studies, Estrogen Replacement Therapy, Female, Heart Failure, Humans, Incidence, Life Style, Middle Aged, Multivariate Analysis, Obesity, Osteoporosis, Postmenopausal, Proportional Hazards Models, Prospective Studies, Risk, Risk Factors, United States, Women{\textquoteright}s Health}, issn = {1540-9996}, doi = {10.1089/154099903765448853}, author = {Rea, Thomas D and Psaty, Bruce M and Heckbert, Susan R and Cushman, Mary and Meilahn, Elaine and Olson, Jean L and Lemaitre, Rozenn N and Smith, Nicholas L and Sotoodehnia, Nona and Chaves, Paulo H M} } @article {759, title = {Lp(a) lipoprotein, vascular disease, and mortality in the elderly.}, journal = {N Engl J Med}, volume = {349}, year = {2003}, month = {2003 Nov 27}, pages = {2108-15}, abstract = {

BACKGROUND: As compared with what is known about predictors of vascular events in middle-aged persons, less is known about these events in the elderly. Lp(a) lipoprotein, which plays an important part in atherothrombogenesis, has been associated with an increased risk of vascular disease. We investigated this relation among older U.S. adults.

METHODS: In a prospective study of 5888 community-dwelling older adults (65 years of age or older) in the United States, 2375 women and 1597 men who were free of vascular disease provided base-line serum samples for analysis for levels of Lp(a) lipoprotein. These 3972 subjects were followed for a median of 7.4 years to evaluate the development of stroke and to track deaths from vascular causes and all causes. The men and women were divided into quintile groups according to the Lp(a) lipoprotein level at base line.

RESULTS: Using Cox proportional-hazards models, we determined the risk associated with each quintile level of Lp(a) lipoprotein, with the lowest quintile serving as the reference group. As compared with those in the lowest quintile, men in the highest quintile had three times the unadjusted risk of stroke (relative risk, 3.00; 95 percent confidence interval, 1.59 to 5.65), almost three times the risk of death associated with vascular events (relative risk, 2.54; 95 percent confidence interval, 1.59 to 4.08), and nearly twice the risk of death from all causes (relative risk, 1.76; 95 percent confidence interval, 1.31 to 2.36). Adjustment for age; sex; the levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides; carotid-wall thickness; smoking status; the presence or absence of diabetes and systolic and diastolic hypertension; body-mass index; and other traditional risk factors had little effect on the final assessments. Similar analyses for women, which also included adjustment for estrogen use or nonuse, revealed no such relation.

CONCLUSIONS: Among older adults in the United States, an elevated level of Lp(a) lipoprotein is an independent predictor of stroke, death from vascular disease, and death from any cause in men but not in women. These data support the use of Lp(a) lipoprotein levels in predicting the risk of these events in older men.

}, keywords = {Aged, Coronary Disease, Female, Humans, Incidence, Lipoprotein(a), Male, Mortality, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, Stroke, Survival Analysis, United States, Vascular Diseases}, issn = {1533-4406}, doi = {10.1056/NEJMoa001066}, author = {Ariyo, Abraham A and Thach, Chau and Tracy, Russell} } @article {722, title = {n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {77}, year = {2003}, month = {2003 Feb}, pages = {319-25}, abstract = {

BACKGROUND: Little is known about the relation of the dietary intake of n-3 polyunsaturated fatty acids, ie, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fatty fish and alpha-linolenic acid from vegetable oils, with ischemic heart disease among older adults.

OBJECTIVE: We investigated the associations of plasma phospholipid concentrations of DHA, EPA, and alpha-linolenic acid as biomarkers of intake with the risk of incident fatal ischemic heart disease and incident nonfatal myocardial infarction in older adults.

DESIGN: We conducted a case-control study nested in the Cardiovascular Health Study, a cohort study of adults aged > or = 65 y. Cases experienced incident fatal myocardial infarction and other ischemic heart disease death (n = 54) and incident nonfatal myocardial infarction (n = 125). Matched controls were randomly selected (n = 179). We measured plasma phospholipid concentrations of n-3 polyunsaturated fatty acids in blood samples drawn approximately 2 y before the event.

RESULTS: A higher concentration of combined DHA and EPA was associated with a lower risk of fatal ischemic heart disease, and a higher concentration of alpha-linolenic acid with a tendency to lower risk, after adjustment for risk factors [odds ratio: 0.32 (95\% CI: 0.13, 0.78; P = 0.01) and 0.52 (0.24, 1.15; P = 0.1), respectively]. In contrast, n-3 polyunsaturated fatty acids were not associated with nonfatal myocardial infarction.

CONCLUSIONS: Higher combined dietary intake of DHA and EPA, and possibly alpha-linolenic acid, may lower the risk of fatal ischemic heart disease in older adults. The association of n-3 polyunsaturated fatty acids with fatal ischemic heart disease, but not with nonfatal myocardial infarction, is consistent with possible antiarrhythmic effects of these fatty acids.

}, keywords = {Aged, alpha-Linolenic Acid, Biomarkers, Case-Control Studies, Cohort Studies, Coronary Disease, Dietary Supplements, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Female, Fish Oils, Humans, Incidence, Male, Myocardial Infarction, Odds Ratio, Phospholipids, Prevalence, Prospective Studies, Risk Factors}, issn = {0002-9165}, doi = {10.1093/ajcn/77.2.319}, author = {Lemaitre, Rozenn N and King, Irena B and Mozaffarian, Dariush and Kuller, Lewis H and Tracy, Russell P and Siscovick, David S} } @article {742, title = {Prospective study of the A455V polymorphism in the thrombomodulin gene, plasma thrombomodulin, and incidence of venous thromboembolism: the LITE Study.}, journal = {J Thromb Haemost}, volume = {1}, year = {2003}, month = {2003 Jan}, pages = {88-94}, abstract = {

Plasma thrombomodulin (soluble TM; sTM) is considered to be a marker of endothelial injury, but a recent report indicated that the relationship of sTM with thrombosis is complex. Venous thromboembolic events were identified in adults in two longitudinal cohort studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, totaling 21 690 participants. After 8 years of follow-up, sTM was measured in baseline plasma of 305 participants who developed venous thrombosis and 607 who did not. Thrombomodulin A455V genotype was determined in 302 cases and 626 controls. There was no difference in the prevalence of the three TM genotypes between cases and controls and no difference in age-adjusted mean values of sTM by genotype. There were no associations of age-adjusted sTM or TMA455V genotype with overall venous thromboembolism or with thrombosis in any subtype of venous thromboembolism.

}, keywords = {Age Factors, Aged, Amino Acid Substitution, Case-Control Studies, Female, Genotype, Humans, Incidence, Male, Polymorphism, Genetic, Prevalence, Prospective Studies, Risk Factors, Thromboembolism, Thrombomodulin, Venous Thrombosis}, issn = {1538-7933}, doi = {10.1046/j.1538-7836.2003.00029.x}, author = {Aleksic, N and Folsom, A R and Cushman, M and Heckbert, S R and Tsai, M Y and Wu, K K} } @article {760, title = {The relation of dietary patterns to future survival, health, and cardiovascular events in older adults.}, journal = {J Clin Epidemiol}, volume = {56}, year = {2003}, month = {2003 Dec}, pages = {1224-35}, abstract = {

BACKGROUND: There have been few long-term follow-up studies of older adults who follow different dietary patterns.

METHODS: We cluster-analyzed data on dietary fat, fiber, protein, carbohydrate, and calorie consumption from the U.S. Cardiovascular Health Study (mean age=73), and examined the relationship of the dietary clusters to outcomes 10 years later.

RESULTS: The five clusters were named "Healthy diet" (relatively high in fiber and carbohydrate and low in fat), "Unhealthy diet" (relatively high in protein and fat, relatively low in carbohydrates and fiber); "High Calorie," "Low Calorie," and "Low 4," which was distinguished by higher alcohol consumption. The clusters were strongly associated with demographic factors, health behaviors, and baseline health status. The Healthy diet cluster had the most years of life and years of healthy life, and the Unhealthy diet cluster had the fewest. The Low 4 cluster had the best cardiovascular outcomes. Differences were not usually large.

CONCLUSIONS: Older adults who followed the healthy eating pattern had somewhat longer and healthier lives, and the cluster with more alcohol consumption was associated with fewer cardiovascular events. The unhealthy eating pattern had the worst outcomes.

}, keywords = {Aged, Cardiovascular Diseases, Cluster Analysis, Diet, Energy Intake, Female, Follow-Up Studies, Health Status, Humans, Incidence, Linear Models, Male, Nutritional Physiological Phenomena, Survival Rate}, issn = {0895-4356}, doi = {10.1016/s0895-4356(03)00202-6}, author = {Diehr, Paula and Beresford, Shirley A A} } @article {803, title = {The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Oct}, pages = {1639-47}, abstract = {

OBJECTIVES: To assess the association between lipid levels and cardiovascular events in older adults.

DESIGN: A prospective population-based study.

SETTING: Four field centers in U.S. communities.

PARTICIPANTS: A total of 5,201 adults aged 65 and older living in U.S. communities, plus a recruitment of 687 African Americans 3 years later.

MEASUREMENTS: Fasting lipid measures included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides.

RESULTS: At baseline, 1,954 men and 2,931 women were at risk for an incident myocardial infarction (MI) or stroke. During an average 7.5-year follow-up, 436 subjects had a coronary event, 332 had an ischemic stroke, 104 a hemorrhagic stroke, and 1,096 died. After adjustment, lipid measures were not major predictors of the outcomes of MI, ischemic stroke, hemorrhagic stroke, and total mortality. For total cholesterol and LDL-C, the associations with MI and ischemic stroke were only marginally significant. HDL-C was inversely associated with MI risk (hazard ratio=0.85 per standard deviation of 15.7 mg/dL, 95\% confidence interval=0.76-0.96). For the outcome of ischemic stroke, high levels of HDL-C were associated with a decreased risk in men but not women. Lipid measures were generally only weakly associated with the risks of hemorrhagic stroke or total mortality.

CONCLUSION: In this population-based study of older adults, most lipid measures were weakly associated with cardiovascular events. The association between low HDL-C and increased MI risk was nonetheless strong and consistent.

}, keywords = {African Americans, African Continental Ancestry Group, Aged, Female, Health Surveys, Humans, Incidence, Lipids, Male, Mortality, Myocardial Infarction, Population Surveillance, Prospective Studies, Risk Factors, Stroke, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52455.x}, author = {Psaty, Bruce M and Anderson, Melissa and Kronmal, Richard A and Tracy, Russell P and Orchard, Trevor and Fried, Linda P and Lumley, Thomas and Robbins, John and Burke, Greg and Newman, Anne B and Furberg, Curt D} } @article {791, title = {The association of fasting glucose levels with congestive heart failure in diabetic adults > or =65 years: the Cardiovascular Health Study.}, journal = {J Am Coll Cardiol}, volume = {43}, year = {2004}, month = {2004 Jun 16}, pages = {2236-41}, abstract = {

OBJECTIVES: The purpose of this study was to determine if fasting glucose levels are an independent risk factor for congestive heart failure (CHF) in elderly individuals with diabetes mellitus (DM) with or without coronary heart disease (CHD).

BACKGROUND: Diabetes mellitus and CHF frequently coexist in the elderly. It is not clear whether fasting glucose levels in the setting of DM are a risk factor for incident CHF in the elderly.

METHODS: A cohort of 829 diabetic participants, age > or =65 years, without prevalent CHF, was followed for five to eight years. The Cox proportional hazards modeling was used to determine the risk of CHF by fasting glucose levels. The cohort was categorized by the presence or absence of prevalent CHD.

RESULTS: For a 1 standard deviation (60.6 mg/dl) increase in fasting glucose, the adjusted hazard ratios for incident CHF among participants without CHD at baseline, with or without an incident myocardial infarction (MI) or CHD event on follow-up, was 1.41 (95\% confidence interval 1.24 to 1.61; p < 0.0001). Among those with prevalent CHD at baseline, with or without another incident MI or CHD event on follow-up, the corresponding adjusted hazard ratio was 1.27 (95\% confidence interval 1.02 to 1.58; p < 0.05).

CONCLUSIONS: Among older adults with DM, elevated fasting glucose levels are a risk factor for incident CHF. The relationship of fasting glucose to CHF differs somewhat by the presence or absence of prevalent CHD.

}, keywords = {Aged, Biomarkers, Blood Glucose, Blood Pressure, Coronary Disease, Diabetes Mellitus, Diabetic Angiopathies, Fasting, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Proportional Hazards Models, Risk Factors, Statistics as Topic, Stroke Volume, Ventricular Function, Left}, issn = {0735-1097}, doi = {10.1016/j.jacc.2003.10.074}, author = {Barzilay, Joshua I and Kronmal, Richard A and Gottdiener, John S and Smith, Nicholas L and Burke, Gregory L and Tracy, Russell and Savage, Peter J and Carlson, Michelle} } @article {773, title = {Chronic renal insufficiency and cardiovascular events in the elderly: findings from the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 Mar-Apr}, pages = {81-90}, abstract = {

In the Cardiovascular Health Study, the authors sought to evaluate the impact of chronic renal insufficiency (CRI) on cardiovascular risk status and outcomes in a representative sample of community-dwelling elderly adults. Defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men, CRI was present in 647 (11\%) of 5808 participants. At baseline, the prevalence of clinical or subclinical cardiovascular disease was 64\% in participants with CRI and 43\% in those without CRI (odds ratio, 2.34; 95\% confidence interval, 1.96-2.80). The incidence of cardiovascular disease events during follow-up was 3\% per year in participants with creatinine levels <1.10 mg/dL and increased steadily to reach 7\% per year in those with creatinine > or =1.70 mg/dL. Among the possible mediators for the association between CRI and cardiovascular morbidity are inflammatory (C-reactive protein, fibrinogen, and interleukin-6) and hemostatic (factor VII, factor VIII, plasmin-antiplasmin product, and D-dimer) biomarkers, all of which were significantly elevated in Cardiovascular Health Study participants with CRI. Future studies should evaluate the contribution of novel and traditional cardiovascular risk factors to the cardiovascular risk of elderly persons with CRI. The identification of CRI in the elderly and the use of cardiovascular prevention therapies represent a major opportunity to reduce their burden of cardiovascular morbidity.

}, keywords = {Aged, Blood Coagulation Factors, Cardiovascular Diseases, Chronic Disease, Creatinine, Cystatin C, Cystatins, Female, Fibrinogen, Geriatric Assessment, Humans, Incidence, Male, Prevalence, Renal Insufficiency, Risk Factors}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02125.x}, author = {Shlipak, Michael G and Fried, Linda F and Stehman-Breen, Catherine and Siscovick, David and Newman, Anne B} } @article {771, title = {Congestive heart failure in the elderly: the Cardiovascular Health Study.}, journal = {Am J Geriatr Cardiol}, volume = {13}, year = {2004}, month = {2004 Mar-Apr}, pages = {61-8}, abstract = {

Congestive heart failure in the elderly is recognized as a national public health priority; however, clinical diagnosis can be problematic in elderly persons, many of whom have a history of heart failure in the presence of normal or only minimally decreased ejection fraction. Findings of the Cardiovascular Health Study have underscored the common substrate and predictors underlying heart failure both with decreased ejection fraction and with normal ejection fraction (i.e., diastolic heart failure). Coronary heart disease, systolic blood pressure, and C-reactive protein (a measure of inflammation) are predictive of heart failure independent of ejection fraction. Left atrial size, arguably a marker of the effects of impaired diastolic filling over time, is increased in both systolic and diastolic heart failure of the elderly, as is atrial natriuretic peptide. The outcome of heart failure in elderly persons is poor both for systolic and diastolic heart failure. Moreover, many community-dwelling elderly persons have decreased ejection fraction without heart failure. In these persons the chance of death is similar to that of participants with diastolic heart failure. Since most clinical trials have studied younger patients with predominantly systolic heart failure, the appropriate therapy for heart failure in elderly persons remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Atrial Natriuretic Factor, Blood Pressure, Diagnosis, Differential, Female, Geriatric Assessment, Heart Atria, Heart Failure, Heart Rate, Humans, Incidence, Male, Prevalence, Risk Factors, Stroke Volume, United States, Ventricular Dysfunction, Left}, issn = {1076-7460}, doi = {10.1111/j.1076-7460.2004.02121.x}, author = {Mathew, Sunil T and Gottdiener, John S and Kitzman, Dalane and Aurigemma, Gerard} } @article {793, title = {Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.}, journal = {Am J Med}, volume = {117}, year = {2004}, month = {2004 Jul 01}, pages = {19-25}, abstract = {

PURPOSE: To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States.

METHODS: The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review.

RESULTS: The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48\% (175/366) of events. The 28-day case-fatality rate was 11\% (29/265) after a first venous thromboembolism and 25\% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7\% per year (95\% confidence interval [CI]: 4.5\% to 10.9\% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95\% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95\% CI: 2.0 to 41.7).

CONCLUSION: The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.

}, keywords = {Aged, Case-Control Studies, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Neoplasms, Population Surveillance, Pulmonary Embolism, Recurrence, Risk Factors, Survival Rate, Venous Thrombosis}, issn = {0002-9343}, doi = {10.1016/j.amjmed.2004.01.018}, author = {Cushman, Mary and Tsai, Albert W and White, Richard H and Heckbert, Susan R and Rosamond, Wayne D and Enright, Paul and Folsom, Aaron R} } @article {797, title = {Fish intake and risk of incident atrial fibrillation.}, journal = {Circulation}, volume = {110}, year = {2004}, month = {2004 Jul 27}, pages = {368-73}, abstract = {

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is particularly common in the elderly. Although effects of fish intake, including potential antiarrhythmic effects, may favorably influence risk of AF, relationships between fish intake and AF incidence have not been evaluated.

METHODS AND RESULTS: In a prospective, population-based cohort of 4815 adults > or =age 65 years, usual dietary intake was assessed at baseline in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. AF incidence was prospectively ascertained on the basis of hospital discharge records and annual electrocardiograms. During 12 years{\textquoteright} follow-up, 980 cases of incident AF were diagnosed. In multivariate analyses, consumption of tuna or other broiled or baked fish was inversely associated with incidence of AF, with 28\% lower risk with intake 1 to 4 times per week (HR=0.72, 95\% CI=0.58 to 0.91, P=0.005), and 31\% lower risk with intake > or =5 times per week (HR=0.69, 95\% CI=0.52 to 0.91, P=0.008), compared with <1 time per month (P trend=0.004). Results were not materially different after adjustment for preceding myocardial infarction or congestive heart failure. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of AF.

CONCLUSIONS: Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower incidence of AF. Fish intake may influence risk of this common cardiac arrhythmia.

}, keywords = {Aged, Animals, Atrial Fibrillation, Cardiotonic Agents, Cohort Studies, Cooking, Diet, Dietary Fats, Fatty Acids, Omega-3, Fish Oils, Fishes, Follow-Up Studies, Humans, Incidence, Massachusetts, Proportional Hazards Models, Prospective Studies, Risk, Seafood, Tuna}, issn = {1524-4539}, doi = {10.1161/01.CIR.0000138154.00779.A5}, author = {Mozaffarian, Dariush and Psaty, Bruce M and Rimm, Eric B and Lemaitre, Rozenn N and Burke, Gregory L and Lyles, Mary F and Lefkowitz, David and Siscovick, David S} } @article {762, title = {Incidence and prevalence of dementia in the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {52}, year = {2004}, month = {2004 Feb}, pages = {195-204}, abstract = {

OBJECTIVES: To estimate the incidence and prevalence of dementia, Alzheimer{\textquoteright}s disease (AD), and vascular dementia (VaD) in the Cardiovascular Health Study (CHS) cohort.

DESIGN: Longitudinal cohort study using prospectively and retrospectively collected data to evaluate dementia.

SETTING: Four U.S. communities.

PARTICIPANTS: There were 3,602 CHS participants, including 2,865 white and 492 African-American participants free of dementia, who completed a cranial magnetic resonance image between 1992 and 1994 and were followed for an average of 5.4 years.

MEASUREMENTS: Dementia was classified by neurologist/psychiatrist committee review using neuropsychological tests, neurological examinations, medical records, physician questionnaires, and proxy/informant interviews. Demographics and apolipoprotein E (APOE) genotype were collected at baseline. Incidence by type of dementia was determined using National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria for AD and Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Center{\textquoteright}s State of California criteria for VaD.

RESULTS: Classification resulted in 227 persons with prevalent dementia at entry into the study and 480 incident cases during follow-up. Incidence rates of dementia scaled to age 80 were 34.7 per 1,000 person-years for white women, 35.3 for white men, 58.8 for African-American women, and 53.0 for African-American men. Sex differences were not significant within race. Adjusted for age and education, racial differences were only of borderline significance and may have been influenced by ascertainment methodology. Rates differed substantially by educational attainment but were only significant for whites. Those with the APOE epsilon4 allele had an incidence rate at age 80 of 56.4, compared with 29.6 for those without this allele (P<.001). In whites, type-specific incidence at age 80 was 19.2 for AD versus 14.6 for VaD. These rates were 34.7 and 27.2 for African Americans. At termination of observation, women had only a slightly higher prevalence of dementia (16.0\%) than men (14.7\%).

CONCLUSION: Sex and racial differences were not found, and VaD was higher than reported in other studies. These data provide new estimates of dementia incidence in a community sample for projection of future burden.

}, keywords = {African Americans, Age Distribution, Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Dementia, Dementia, Vascular, Education, European Continental Ancestry Group, Female, Humans, Incidence, Longitudinal Studies, Male, Prevalence, Proportional Hazards Models, Risk Factors, Sex Distribution, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2004.52058.x}, author = {Fitzpatrick, Annette L and Kuller, Lewis H and Ives, Diane G and Lopez, Oscar L and Jagust, William and Breitner, John C S and Jones, Beverly and Lyketsos, Constantine and Dulberg, Corinne} } @article {764, title = {Prevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons. The Cardiovascular Health Study (CHS E-131).}, journal = {J Am Coll Cardiol}, volume = {43}, year = {2004}, month = {2004 Jan 21}, pages = {187-93}, abstract = {

OBJECTIVES: We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT).

BACKGROUND: Common carotid artery intima-media thickness has been associated with the incidence of cardiovascular disease.

METHOD: Noninvasive measurements of IMT were made with high-resolution ultrasonography in 5,640 subjects 65 years of age or older participating in the Cardiovascular Health Study. New coronary and/or cerebrovascular events served as outcome variables over a median 10.2-year follow-up. To characterize different carotid structural geometric patterns (CGP), vascular mass (VM) was combined with the wall-to-lumen ratio (W/L). Normal values for W/L and VM were defined as age-adjusted, gender-specific 75th percentiles of the 1,899 normotensive subjects free of CVD at baseline. Four CGPs were defined: CGP1 = normal W/L ratio and VM; CGP2 = arterial remodeling (i.e., increased W/L ratio with normal VM); CGP3 = arterial hypertrophy (i.e., increased W/L ratio with increased VM); and CGP4 = arterial hypertrophy with dilation (i.e., normal W/L ratio and increased VM).

RESULTS: Coronary or cerebrovascular events (adjusted for age, gender, traditional risk factors, and IMT) were associated with CGP in subjects free of CVD at baseline. Specifically, the hazard ratio (Cox proportional-hazards analyses) for CGP3 (arterial hypertrophy) was 1.25 (95\% confidence interval [CI] 1.03 to 1.53), and for CGP4 (arterial hypertrophy with dilation) was 1.43 (95\% CI 1.16 to 1.75) compared with CGP1 (normal).

CONCLUSIONS: Arterial hypertrophy defined by variant CGP patterns is associated with the development of new CVD, independent of age, traditional risk factors, and CCA IMT.

}, keywords = {Aged, Cardiovascular Diseases, Carotid Arteries, Female, Humans, Hypertrophy, Incidence, Male, Predictive Value of Tests, Prevalence, Prospective Studies, Ultrasonography}, issn = {0735-1097}, doi = {10.1016/j.jacc.2003.08.035}, author = {Scuteri, Angelo and Manolio, Teri A and Marino, Emily K and Arnold, Alice M and Lakatta, Edward G} } @article {789, title = {The relationship of fasting serum radioimmune insulin levels to incident coronary heart disease in an insulin-treated diabetic cohort.}, journal = {J Clin Endocrinol Metab}, volume = {89}, year = {2004}, month = {2004 Jun}, pages = {2852-8}, abstract = {

It is not known whether insulin levels, in the setting of insulin treatment, are an independent risk factor for coronary heart disease (CHD). We studied a cohort of 116 insulin-treated individuals, 65 yr or older, who were followed for 5.6-9 yr. All were free of CHD at baseline. There were 47 incident CHD events. In Cox proportional hazards modeling, with fasting immune-reactive insulin levels as a continuous variable, the hazard ratio for CHD was statistically significant (P < 0.0001). When insulin levels were divided into intervals, those in the third interval [43-150 microU/ml (258-900 pmol/liter)] had an adjusted 30\% increased relative risk (95\% confidence interval, 0.57, 2.98) compared with those in the first interval [<20 microU/ml (<120 pmol/liter)]. Those in the fourth interval [151-400 microU/ml (906-2400 pmol/liter)] had an adjusted 5.6-fold increased risk (2.3-13.1; P < 0.0001). Approximately 15\% of the cohort had such elevated insulin levels. Immune-reactive insulin levels were strongly correlated with specific insulin, proinsulin, and insulin antibody levels. Markedly elevated fasting immune-reactive insulin levels were an independent risk factor for CHD in this study of insulin-treated older adults. These observational findings should be confirmed through larger prospective studies, given their implications for insulin therapy.

}, keywords = {Aged, Cohort Studies, Coronary Disease, Diabetes Mellitus, Type 1, Fasting, Female, Follow-Up Studies, Humans, Hypoglycemic Agents, Incidence, Insulin, Male, Radioimmunoassay, Risk Factors}, issn = {0021-972X}, doi = {10.1210/jc.2003-031822}, author = {Kronmal, Richard A and Barzilay, Joshua I and Tracy, Russell P and Savage, Peter J and Orchard, Trevor J and Burke, Gregory L} } @article {801, title = {Stroke risk factors and loss of high cognitive function.}, journal = {Neurology}, volume = {63}, year = {2004}, month = {2004 Sep 14}, pages = {793-9}, abstract = {

BACKGROUND: Modifiable stroke risk factors may contribute to age-associated declines in cognitive function. Individuals with high levels of cognitive function after midlife may have less exposure to these stroke risk factors or may be less susceptible to their effects on cognition.

METHODS: The Cardiovascular Health Study (CHS)* is a population-based, longitudinal cohort study of 5,888 people age 65 years and older. Participants (n = 4,129) who were free of dementia, stroke, or TIA at the time of baseline cranial MRI were selected for analysis. High cognitive function at baseline was defined by performance at or above midlife norms on the Modified Mini-Mental State Examination (3MS).

RESULTS: The odds of having high cognitive function at baseline decreased by quartile of stroke risk (highest vs lowest risk quartile, adjusted odds ratio [OR] 0.68; 95\% CI 0.52 to 0.88; p for trend = 0.005). Stroke risk was a predictor of decline on the 3MS in those with typical levels of cognitive function at baseline, even in the absence of incident stroke or TIA (highest vs lowest risk quartile for 3MS decline, adjusted OR 2.11; 95\% CI 1.42 to 3.13; p for trend < 0.001). In contrast, stroke risk was not associated with decline on the 3MS in those with high cognitive function at baseline (p = 0.03 for interaction).

CONCLUSIONS: In a cohort of older adults without stroke, TIA, or dementia, cognitive function and incident cognitive decline were associated with risk for stroke. Additional studies are needed to determine whether modification of stroke risk factors can reduce the cognitive decline that is often attributed to normal aging.

}, keywords = {Aged, Aged, 80 and over, Aging, Cognition Disorders, Cohort Studies, Comorbidity, Female, Follow-Up Studies, Higher Nervous Activity, Humans, Incidence, Male, Risk Assessment, Risk Factors, Sampling Studies, Sensitivity and Specificity, Severity of Illness Index, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000137014.36689.7f}, author = {Elkins, J S and O{\textquoteright}Meara, E S and Longstreth, W T and Carlson, M C and Manolio, T A and Johnston, S C} } @article {802, title = {Survival associated with two sets of diagnostic criteria for congestive heart failure.}, journal = {Am J Epidemiol}, volume = {160}, year = {2004}, month = {2004 Oct 01}, pages = {628-35}, abstract = {

Congestive heart failure (CHF) definitions vary across epidemiologic studies. The Framingham Heart Study criteria include CHF signs and symptoms assessed by a physician panel. In the Cardiovascular Health Study, a committee of physicians adjudicated CHF diagnoses, confirmed by signs, symptoms, clinical tests, and/or medical therapy. The authors used data from the Cardiovascular Health Study, a population-based cohort study of 5,888 elderly US adults, to compare CHF incidence and survival patterns following onset of CHF as defined by Framingham and/or Cardiovascular Health Study criteria. They constructed an inception cohort of nonfatal, hospitalized CHF patients. Of 875 participants who had qualifying CHF hospitalizations between 1989 and 2000, 54\% experienced a first CHF event that fulfilled both sets of diagnostic criteria (concordant), 31\% fulfilled only the Framingham criteria (Framingham only), and 15\% fulfilled only the Cardiovascular Health Study criteria (Cardiovascular Health Study only). No significant survival difference was found between the Framingham-only group (hazard ratio = 0.87, 95\% confidence interval: 0.71, 1.07) or the Cardiovascular Health Study-only group (hazard ratio = 0.89, 95\% confidence interval: 0.68, 1.15) and the concordant group (referent). Compared with Cardiovascular Health Study central adjudication, Framingham criteria for CHF identified a larger group of participants with incident CHF, but all-cause mortality rates were similar across these diagnostic classifications.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Diagnosis, Differential, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Prognosis, Severity of Illness Index, Survival Analysis}, issn = {0002-9262}, doi = {10.1093/aje/kwh268}, author = {Schellenbaum, Gina D and Rea, Thomas D and Heckbert, Susan R and Smith, Nicholas L and Lumley, Thomas and Roger, Veronique L and Kitzman, Dalane W and Taylor, Herman A and Levy, Daniel and Psaty, Bruce M} } @article {821, title = {Association between screening for osteoporosis and the incidence of hip fracture.}, journal = {Ann Intern Med}, volume = {142}, year = {2005}, month = {2005 Feb 01}, pages = {173-81}, abstract = {

BACKGROUND: Because direct evidence for the effectiveness of screening is lacking, guidelines disagree on whether people should be screened for osteoporosis.

OBJECTIVE: To determine whether population-based screening for osteoporosis in older adults is associated with fewer incident hip fractures than usual medical care.

DESIGN: Nonconcurrent cohort study.

SETTING: Population-based cohort enrolled in the Cardiovascular Health Study (CHS) from 4 states (California, Pennsylvania, Maryland, and North Carolina).

PATIENTS: 3107 adults 65 years of age and older who attended their CHS study visits in 1994-1995.

MEASUREMENTS: 31 participant characteristics (including demographic characteristics, medical histories, medications, and physical examination findings) and incident hip fractures over 6 years of follow-up.

INTERVENTION: Bone density scans (dual-energy x-ray absorptiometry [DEXA] at the hip) for participants in California and Pennsylvania (n = 1422) and usual care for participants in Maryland and North Carolina (n = 1685).

RESULTS: The incidence of hip fractures per 1000 person-years was 4.8 in the screened group and 8.2 in the usual care group. Screening was associated with a statistically significant lower hazard of hip fracture than usual care after adjustment for sex and propensity to be screened (Cox proportional hazard ratio, 0.64 [95\% CI, 0.41 to 0.99]).

LIMITATIONS: The mechanism of the association was unclear. A small unmeasured confounder that decreased the hazard of hip fracture could diminish or erase the observed association.

CONCLUSIONS: Use of hip DEXA scans to screen for osteoporosis in older adults was associated with 36\% fewer incident hip fractures over 6 years compared with usual medical care. Further research is needed to explore the mechanism of this association.

}, keywords = {Absorptiometry, Photon, Aged, Aged, 80 and over, Cohort Studies, Female, Hip Fractures, Humans, Incidence, Male, Mass Screening, Osteoporosis, Risk Factors, Sensitivity and Specificity}, issn = {1539-3704}, doi = {10.7326/0003-4819-142-3-200502010-00007}, author = {Kern, Lisa M and Powe, Neil R and Levine, Michael A and Fitzpatrick, Annette L and Harris, Tamara B and Robbins, John and Fried, Linda P} } @article {870, title = {Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1409-14}, abstract = {

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).

METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician{\textquoteright}s assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.

RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28\% (95\% CI: 0.51 to 1.02), and AD by 41\% (95\% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.

CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Dementia, Dietary Fats, Unsaturated, Fatty Acids, Omega-3, Feeding Behavior, Female, Fish Oils, Fish Products, Food, Formulated, Genetic Predisposition to Disease, Humans, Incidence, Male, Risk Factors, Socioeconomic Factors, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000183148.34197.2e}, author = {Huang, T L and Zandi, P P and Tucker, K L and Fitzpatrick, A L and Kuller, L H and Fried, L P and Burke, G L and Carlson, M C} } @article {825, title = {beta(2)-Adrenergic receptor polymorphisms and determinants of cardiovascular risk: the Cardiovascular Health Study.}, journal = {Am J Hypertens}, volume = {18}, year = {2005}, month = {2005 Mar}, pages = {392-7}, abstract = {

BACKGROUND: Common Arg16Gly and Gln27Glu polymorphisms of the beta(2)-adrenergic receptor (beta(2)AR) have been associated with hypertension and coronary disease. This analysis of older adults in the Cardiovascular Health Study examined whether these polymorphisms were associated with blood pressure (BP), subclinical atherosclerosis, and, among treated hypertensive individuals, differences in coronary disease risk according to antihypertensive drug class.

METHODS: Altogether, 5249 participants (4441 white and 808 African American, median follow-up time 10.2 years) were genotyped for both polymorphisms. Ankle-arm index (AAI), carotid intima-media thickness (IMT), and brachial flow-mediated dilation were measured cross-sectionally. All estimates were adjusted for ethnicity.

RESULTS: Relative to Gln27 homozygotes, carrying the Glu27 allele was not associated with new-onset hypertension (hazard ratio [HR] = 1.01, 95\% confidence interval [CI] = 0.87 to 1.16), BP control (odds ratio [OR] = 0.97, 95\% CI = 0.89 to 1.06), AAI (mean difference 0.0042 +/- 0.0052), carotid IMT (mean difference 0.0044 +/- 0.02 mm), or brachial flow-mediated dilation (mean difference in baseline diameter -0.028 +/- 0.036 mm; the most marked of three measures). Among treated hypertensive individuals, coronary disease risk was similar in Glu27 carriers relative to Gln27 homozygotes in subgroups defined by use of beta-blockers (HR = 1.09, 95\% CI = 0.64 to 1.87) or other antihypertensive medications (HR = 1.00, 95\% CI = 0.78 to 1.28). Results were similar for the Arg16Gly polymorphism.

CONCLUSIONS: The association of beta(2)AR genotype with coronary disease previously reported in this older adult population is not likely to be explained by BP levels, subclinical atherosclerosis, or antihypertensive treatment. Other measures of vascular response, gene-gene or gene-environment interactions, or characteristics developing earlier in life may mediate the association between beta(2)AR genotype and coronary disease and merit further research.

}, keywords = {African Americans, Antihypertensive Agents, Arteriosclerosis, Coronary Artery Disease, European Continental Ancestry Group, Female, Genotype, Homozygote, Humans, Hypertension, Incidence, Male, Middle Aged, Polymorphism, Genetic, Receptors, Adrenergic, beta-2, Risk Factors}, issn = {0895-7061}, doi = {10.1016/j.amjhyper.2004.10.014}, author = {Hindorff, Lucia A and Heckbert, Susan R and Psaty, Bruce M and Lumley, Thomas and Siscovick, David S and Herrington, David M and Edwards, Karen L and Tracy, Russell P} } @article {845, title = {C-reactive protein and the 10-year incidence of coronary heart disease in older men and women: the cardiovascular health study.}, journal = {Circulation}, volume = {112}, year = {2005}, month = {2005 Jul 05}, pages = {25-31}, abstract = {

BACKGROUND: High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available.

METHODS AND RESULTS: Baseline CRP was measured in 3971 men and women > or =65 years of age without prior vascular diseases; 26\% had elevated concentrations (>3 mg/L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33\% in men and 17\% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP >3 mg/L compared with <1 mg/L was 1.82 (95\% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 (95\% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11\%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10\% to 20\%, the observed CHD incidence was 32\% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk >20\%; the incidences were 31\% and 10\% for elevated and normal CRP levels, respectively.

CONCLUSIONS: In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, C-Reactive Protein, Coronary Disease, Female, Humans, Incidence, Inflammation, Male, Myocardial Infarction, Predictive Value of Tests, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.104.504159}, author = {Cushman, Mary and Arnold, Alice M and Psaty, Bruce M and Manolio, Teri A and Kuller, Lewis H and Burke, Gregory L and Polak, Joseph F and Tracy, Russell P} } @article {862, title = {Cystatin C and subclinical brain infarction.}, journal = {J Am Soc Nephrol}, volume = {16}, year = {2005}, month = {2005 Dec}, pages = {3721-7}, abstract = {

Subclinical brain infarcts (SBI) are common in the elderly and are associated with covert neurologic and cognitive impairment. Although renal impairment is associated with accelerated cerebrovascular disease and an increased risk for clinically apparent brain infarct, few studies have examined the relationship between renal function and SBI, and these may have been limited by the inaccuracy of creatinine as a renal function marker. A cross-sectional study was performed among older adults in the Cardiovascular Health Study to examine associations between SBI and two serum markers of renal function: Serum creatinine (SCr) and cystatin C (CysC). Patients had cranial magnetic resonance imaging and renal markers measured in 1992 to 1993. Logistic regression was used to estimate the associations between renal function (estimated by 1/SCr and 1/CysC) and SBI, controlling for potential confounding factors. SBI were present in 789 (28.7\%) of 2784 participants. A linear association with SBI was observed for 1/CysC (per 1-SD decrement; odds ratio [OR] 1.20; 95\% confidence interval [CI] 1.09 to 1.32; P < 0.001) but not for 1/SCr (OR 1.08; 95\% CI 0.98 to 1.19; P = 0.14), for which a quadratic U-shaped association was suggested (P = 0.004). In a model with both markers, 1/CysC was linearly associated with SBI (OR 1.26; P < 0.001), whereas 1/SCr was not (OR 1.06; P = 0.3). The prevalence of SBI was directly associated with quintile of CysC, whereas the association between SCr and SBI was U-shaped, with greater prevalence at high and low levels. Compared with creatinine, CysC, a novel marker of renal function, has a stronger and more direct association with SBI in the elderly.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Brain Infarction, Confidence Intervals, Creatinine, Cross-Sectional Studies, Cystatin C, Cystatins, Disease Progression, Female, Geriatric Assessment, Humans, Incidence, Ischemic Attack, Transient, Magnetic Resonance Imaging, Male, Odds Ratio, Predictive Value of Tests, Prognosis, Risk Assessment, Sensitivity and Specificity, Severity of Illness Index, Sex Factors, Survival Analysis}, issn = {1046-6673}, doi = {10.1681/ASN.2005010006}, author = {Seliger, Stephen L and Longstreth, W T and Katz, Ronit and Manolio, Teri and Fried, Linda F and Shlipak, Michael and Stehman-Breen, Catherine O and Newman, Anne and Sarnak, Mark and Gillen, Daniel L and Bleyer, Anthony and Siscovick, David S} } @article {827, title = {Cystatin C concentration as a risk factor for heart failure in older adults.}, journal = {Ann Intern Med}, volume = {142}, year = {2005}, month = {2005 Apr 05}, pages = {497-505}, abstract = {

BACKGROUND: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function.

OBJECTIVE: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure.

DESIGN: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months.

SETTING: Adults 65 years of age or older from 4 communities in the United States.

PARTICIPANTS: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine.

MEASUREMENTS: Incident heart failure.

RESULTS: The mean (+/-SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 micromol/L (1.01 +/- 0.39 mg/dL), respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17\%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95\% CI, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [CI, 0.59 to 1.01], 0.85 [CI, 0.64 to 1.13], 0.97 [CI, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.49]).

LIMITATIONS: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear.

CONCLUSIONS: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. *For a full list of participating Cardiovascular Health Study investigators and institutions, see http://www.chs-nhlbi.org.

}, keywords = {Aged, Biomarkers, Creatinine, Cystatin C, Cystatins, Female, Follow-Up Studies, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney, Kidney Function Tests, Male, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-142-7-200504050-00008}, author = {Sarnak, Mark J and Katz, Ronit and Stehman-Breen, Catherine O and Fried, Linda F and Jenny, Nancy Swords and Psaty, Bruce M and Newman, Anne B and Siscovick, David and Shlipak, Michael G} } @article {833, title = {Factors associated with incidence and persistence of symptoms of disturbed sleep in an elderly cohort: the Cardiovascular Health Study.}, journal = {Am J Med Sci}, volume = {329}, year = {2005}, month = {2005 Apr}, pages = {163-72}, abstract = {

BACKGROUND: There are limited data pertaining to the factors influencing the incidence and persistence of sleep symptoms in the elderly. The purpose of this study was to determine the incidence and nonremission rates of the following sleep symptoms: trouble falling asleep (TFA), frequent awakenings (FA), and excessive daytime sleepiness (EDS) in the Cardiovascular Health Study (CHS), a prospective multicenter study of cardiovascular disease in a large cohort of elderly adults. Factors influencing these rates were assessed as well.

METHODS: 4467 participants in CHS were surveyed for the presence of TFA, FA, and EDS as well as other health problems at their baseline examination and at a follow-up examination 1 to 4 years later.

RESULTS: Annualized incidence and nonremission rates were the following: TFA (2.8\% and 15.4\%), FA (12.3\% and 22.7\%), and EDS (4.4\% and 13.4\%). Women were more likely to have incident and persistent TFA. Depression was the primary factor predicting the incidence of all three sleep symptoms. However, other health conditions, including respiratory symptoms and cardiovascular disease, and limitation in activities of daily living were important as well. Depression also was the most important factor associated with persistence of these sleep symptoms. The role of other health conditions in determining nonremission was much more limited.

CONCLUSIONS: Incidence of sleep disturbances in the elderly is related to depression, health conditions, and physical functioning. However, persistence of sleep disturbances is best predicted by the presence of depression.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Depression, Female, Health Status, Humans, Incidence, Logistic Models, Male, Odds Ratio, Prevalence, Risk Factors, Sex Factors, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires}, issn = {0002-9629}, doi = {10.1097/00000441-200504000-00001}, author = {Quan, Stuart F and Katz, Ronit and Olson, Jean and Bonekat, William and Enright, Paul L and Young, Terry and Newman, Anne} } @article {818, title = {Fish consumption and stroke risk in elderly individuals: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {200-6}, abstract = {

BACKGROUND: Associations between fish consumption and stroke risk have been inconsistent, possibly because of the differences in types of fish meals consumed. Additionally, such relationships have not been specifically evaluated in the elderly, in whom disease burden may be high and diet less influential.

METHODS: Among 4775 adults 65 years or older (range, 65-98 years) and free of known cerebrovascular disease at baseline in 1989-1990, usual dietary intake was assessed using a food frequency questionnaire. In a subset, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches (fish burgers), correlated with plasma phospholipid long-chain n-3 fatty acid levels. Incident strokes were prospectively ascertained.

RESULTS: During 12 years of follow-up, participants experienced 626 incident strokes, including 529 ischemic strokes. In multivariate analyses, tuna/other fish consumption was inversely associated with total stroke (P = .04) and ischemic stroke (P = .02), with 27\% lower risk of ischemic stroke with an intake of 1 to 4 times per week (hazard ratio [HR], 0.73; 95\% confidence interval [CI], 0.55-0.98) and 30\% lower risk with intake of 5 or more times per week (HR, 0.70; 95\% CI, 0.50-0.99) compared with an intake of less than once per month. In contrast, fried fish/fish sandwich consumption was positively associated with total stroke (P = .006) and ischemic stroke (P = .003), with a 44\% higher risk of ischemic stroke with consumption of more than once per week (HR, 1.44; 95\% CI, 1.12-1.85) compared with consumption of less than once per month. Fish consumption was not associated with hemorrhagic stroke.

CONCLUSIONS: Among elderly individuals, consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke, while intake of fried fish or fish sandwiches is associated with higher risk. These results suggest that fish consumption may influence stroke risk late in life; potential mechanisms and alternate explanations warrant further study.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Animals, Cohort Studies, Confidence Intervals, Diet, Fatty Acids, Omega-3, Female, Fish Oils, Fishes, Humans, Incidence, Male, Multivariate Analysis, Probability, Proportional Hazards Models, Risk Assessment, Seafood, Sensitivity and Specificity, Sex Distribution, Stroke, Surveys and Questionnaires, Survival Rate, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.200}, author = {Mozaffarian, Dariush and Longstreth, W T and Lemaitre, Rozenn N and Manolio, Teri A and Kuller, Lewis H and Burke, Gregory L and Siscovick, David S} } @article {843, title = {Fish intake and risk of incident heart failure.}, journal = {J Am Coll Cardiol}, volume = {45}, year = {2005}, month = {2005 Jun 21}, pages = {2015-21}, abstract = {

OBJECTIVES: Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure (CHF).

BACKGROUND: The incidence and health burden of CHF are rising, particularly in older persons. Although n-3 fatty acids have effects that could favorably influence risk of CHF, the relation between fish intake and CHF incidence is unknown.

METHODS: Among 4,738 adults age > or =65 years and free of CHF at baseline in 1989-90, usual dietary intake was assessed using a food frequency questionnaire. In a participant subsample, consumption of tuna or other broiled or baked fish, but not fried fish, correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was prospectively adjudicated.

RESULTS: During 12 years{\textquoteright} follow-up, 955 participants developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was inversely associated with incident CHF, with 20\% lower risk with intake 1 to 2 times/week (hazard ratio [HR] = 0.80, 95\% confidence interval [CI] = 0.64 to 0.99), 31\% lower risk with intake 3 to 4 times/week (HR = 0.69, 95\% CI = 0.52 to 0.91), and 32\% lower risk with intake > or =5 times/week (HR = 0.68, 95\% CI = 0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar analyses, fried fish consumption was positively associated with incident CHF (p trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF (p trend = 0.009), with 37\% lower risk in the highest quintile of intake (HR = 0.73, 95\% CI = 0.57 to 0.94) compared with the lowest.

CONCLUSIONS: Among older adults, consumption of tuna or other broiled or baked fish, but not fried fish, is associated with lower incidence of CHF. Confirmation in additional studies and evaluation of potential mechanisms is warranted.

}, keywords = {Aged, Animals, Cohort Studies, Cooking, Diet, Diet Surveys, Disease-Free Survival, Female, Fishes, Heart Failure, Humans, Incidence, Male, Risk Factors, United States}, issn = {0735-1097}, doi = {10.1016/j.jacc.2005.03.038}, author = {Mozaffarian, Dariush and Bryson, Chris L and Lemaitre, Rozenn N and Burke, Gregory L and Siscovick, David S} } @article {812, title = {Incidence, manifestations, and predictors of worsening white matter on serial cranial magnetic resonance imaging in the elderly: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {36}, year = {2005}, month = {2005 Jan}, pages = {56-61}, abstract = {

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) scans in the elderly commonly show white matter findings that may raise concerns. We sought to document incidence, manifestations, and predictors of worsening white matter grade on serial imaging.

METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people aged 65 years and older, of whom 1919 have had extensive initial and follow-up evaluations, including 2 MRI scans separated by 5 years. Scans were read without clinical information in standard side-by-side fashion to determine worsening white matter grade.

RESULTS: Worsening was evident in 538 participants (28\%), mostly (85\%) by 1 grade. Although similar at initial scan, participants with worsening white matter grade, compared with those without, experienced greater decline on modified Mini-Mental State examination and Digit-Symbol Substitution test (both P< or =0.001) after controlling for potential confounding factors, including occurrence of transient ischemic attack or stroke between scans. Independent predictors of worsening white matter grade included cigarette smoking before initial scan and infarct on initial scan. Otherwise, predictors differed according to white matter grade on initial scan. For low initial grade, increased age, increased diastolic blood pressure, increased high-density lipoprotein cholesterol, and decreased low-density lipoprotein cholesterol were associated with increased risk of worsening. For high initial grade, any cardiovascular disease and low ankle-arm index were associated with decreased risk of worsening, whereas use of diuretics and statins were associated with increased risk.

CONCLUSIONS: Worsening white matter grade on serial MRI scans in elderly is common, is associated with cognitive decline, and has complex relations with cardiovascular risk factors.

}, keywords = {Aged, Brain, Cardiovascular Diseases, Cognition Disorders, Female, Humans, Incidence, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Risk Factors, Stroke}, issn = {1524-4628}, doi = {10.1161/01.STR.0000149625.99732.69}, author = {Longstreth, W T and Arnold, Alice M and Beauchamp, Norman J and Manolio, Teri A and Lefkowitz, David and Jungreis, Charles and Hirsch, Calvin H and O{\textquoteright}Leary, Daniel H and Furberg, Curt D} } @article {820, title = {Incidence of cardiovascular disease in older Americans: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Feb}, pages = {211-8}, abstract = {

OBJECTIVES: To estimate incidence rates of major cardiovascular disease (CVD) in older Americans.

DESIGN: Longitudinal cohort study using prospectively collected data on cardiovascular events.

SETTING: Four U.S. communities in the Cardiovascular Health Study (CHS).

PARTICIPANTS: Five thousand eight hundred eighty-eight participants in CHS, aged 65 or older at enrollment, including 3,393 women (581 African American) and 2,495 men (343 African American).

MEASUREMENTS: At semiannual contacts, participants reported any occurrence of clinical CVD. Medical records were obtained and adjudicated to confirm diagnosis of CVD.

RESULTS: During 10 years of follow-up, incidence of coronary heart disease (CHD) per 1,000 person-years was 39.6 (95\% confidence interval (CI)=36.4-43.1) in men and 22.3 (95\% CI=20.4-24.2) in women. Cumulative event rates for CHD and myocardial infarction for women aged 75 and older at baseline were similar to those for men aged 65 to 74. The overall incidence of stroke was similar for men and women (14.7 (95\% CI=13.0-16.6) and 13.7 (95\% CI=12.4-15.1) per 1,000 person-years, respectively), but the risk of stroke increased with age more rapidly in women, resulting in a greater cumulative event rate for stroke in women than in men aged 75 and older. The incidence of congestive heart failure increased 9\% with each year of age over 65 and was greater than 6\% per year in Caucasian men and women aged 85 and older at baseline. Rates were similar in African Americans and Caucasians.

CONCLUSION: The occurrence of new CVD in older Americans is high, indicating that preventive efforts need to be maintained into older ages.

}, keywords = {African Americans, Age Distribution, Aged, Aged, 80 and over, Cardiovascular Diseases, European Continental Ancestry Group, Female, Geriatric Assessment, Humans, Incidence, Longitudinal Studies, Male, Sex Distribution, Survival Rate, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53105.x}, author = {Arnold, Alice M and Psaty, Bruce M and Kuller, Lewis H and Burke, Gregory L and Manolio, Teri A and Fried, Linda P and Robbins, John A and Kronmal, Richard A} } @article {810, title = {Prostate carcinoma incidence in relation to prediagnostic circulating levels of insulin-like growth factor I, insulin-like growth factor binding protein 3, and insulin.}, journal = {Cancer}, volume = {103}, year = {2005}, month = {2005 Jan 01}, pages = {76-84}, abstract = {

BACKGROUND: There have been several epidemiologic studies investigating the association between circulating levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGFBP-3), and insulin in relation to the risk of prostate carcinoma, with conflicting results. To examine this issue further, the authors conducted a nested case-control study within the Cardiovascular Health Study cohort.

METHODS: In men who were diagnosed with prostate carcinoma (cases) between 1990 and 1999 (n=174), the levels of IGF-I, IGFBP-3, and insulin were measured on blood samples that were obtained 1-9 years prior to diagnosis (mean, 3.4 years). Similar measurements were made on 174 male participants without prostate carcinoma (controls) who were matched to cases based on the year blood was drawn, survival until the date of diagnosis, race, and age.

RESULTS: Relative to the men with IGF-I levels in the first (lowest) quartile of the distribution, the risk of prostate carcinoma for men in the second, third, and fourth (upper) quartiles were 0.77 (95\% confidence interval [95\% CI], 0.43-1.38), 0.73 (95\% CI, 0.41-1.30), and 0.67 (95\% CI, 0.37-1.25), respectively. The results were influenced little by adjustment for levels of IGFBP-3 or, instead, by evaluating the molar IGF-I/IGFBP-3 ratio. An analysis that was restricted to men who had plasma prostate-specific antigen levels <4 ng/mL at the time of the blood draw yielded similar results. The corresponding relative risks for IGFBP-3 were 0.91 (95\% CI, 0.49-1.68), 0.47 (95\% CI, 0.25-0.94), and 0.65 (95\% CI, 0.35-1.20), respectively. The distribution of serum insulin levels in cases and controls were nearly identical.

CONCLUSIONS: The IGF-I level was not associated positively with the risk of prostate carcinoma; however, an increase in the IGFBP-3 level was associated with a modest decrease in risk.

}, keywords = {Aged, Aged, 80 and over, Carcinoma, Case-Control Studies, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Prostatic Neoplasms, Risk Factors}, issn = {0008-543X}, doi = {10.1002/cncr.20727}, author = {Chen, Chu and Lewis, S Kay and Voigt, Lynda and Fitzpatrick, Annette and Plymate, Stephen R and Weiss, Noel S} } @article {819, title = {Renovascular disease and the risk of adverse coronary events in the elderly: a prospective, population-based study.}, journal = {Arch Intern Med}, volume = {165}, year = {2005}, month = {2005 Jan 24}, pages = {207-13}, abstract = {

BACKGROUND: Renovascular disease is a cause of secondary hypertension and renal insufficiency and is suspected to contribute to morbidity and mortality of coronary heart disease. This investigation prospectively examined associations between renovascular disease and adverse coronary events among a population-based sample of elderly Americans.

METHODS: The Cardiovascular Health Study is a prospective, multicenter cohort study of cardiovascular disease risk factors, morbidity, and mortality among Americans older than 65 years. Renal duplex sonography was performed on 870 individuals between January 1995 and February 1997. Renovascular disease was defined as any focal peak systolic velocity of 1.8 m/s or greater (renal artery stenosis) or the absence of a Doppler-shifted signal from an imaged artery (renal artery occlusion). Adverse coronary events were defined as hospitalized angina, fatal or nonfatal myocardial infarction, and coronary revascularization.

RESULTS: During a mean follow-up of 14 months, 68 participants experienced incident or recurrent adverse coronary events. The presence of renovascular disease demonstrated a significant relationship with adverse coronary events (hazard ratio, 1.96; 95\% confidence interval, 1.00-3.83; P = .05) that remained after controlling for the effects of coexisting atherosclerotic risk factors and prevalent cardiovascular disease. The relationship between renovascular disease and adverse coronary events was not dependent on the effects of increased blood pressure.

CONCLUSIONS: The presence of renovascular disease was associated with an increase in the risk of adverse coronary events in this sample. The increment in risk was not dependent on the effects of associated atherosclerotic risk factors, other prevalent cardiovascular disease, or increased blood pressure.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Cohort Studies, Comorbidity, Coronary Disease, Female, Geriatric Assessment, Heart Function Tests, Humans, Hypertension, Renovascular, Incidence, Kidney Function Tests, Male, Multivariate Analysis, Probability, Prognosis, Prospective Studies, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Rate, Ultrasonography, Doppler, United States}, issn = {0003-9926}, doi = {10.1001/archinte.165.2.207}, author = {Edwards, Matthew S and Craven, Timothy E and Burke, Gregory L and Dean, Richard H and Hansen, Kimberley J} } @article {830, title = {Subclinical brain magnetic resonance imaging abnormalities predict physical functional decline in high-functioning older adults.}, journal = {J Am Geriatr Soc}, volume = {53}, year = {2005}, month = {2005 Apr}, pages = {649-54}, abstract = {

OBJECTIVES: To determine whether severity of subclinical brain magnetic resonance imaging (MRI) abnormalities predicts incident self-reported physical impairment or rate of decline in motor performance.

DESIGN: Longitudinal analysis, average follow-up time: 4.0 years.

SETTING: Cardiovascular Health Study (CHS).

PARTICIPANTS: CHS participants with modified Mini-Mental State Examination (3MS) score of 80 or greater, no self-reported disability, no history of stroke, and at least one assessment of mobility (n=2,450, mean age=74.4).

MEASUREMENTS: Brain MRI abnormalities (ventricular enlargement, white matter hyperintensities, subcortical and basal ganglia small brain infarcts), self-reported physical impairment (difficulty walking half a mile or with one or more activities of daily living), and motor performance (gait speed, timed chair stand).

RESULTS: After adjusting for demographics, cardiovascular risk factors, and diseases, risk of incident self-reported physical impairment was 35\% greater for those with severe ventricular enlargement than for those with minimal ventricular enlargement, 22\% greater for those with moderate white matter hyperintensities than for those with minimal white matter hyperintensities, and 26\% greater for participants with at least one brain infarct than for those with no infarcts. Those with moderate to severe brain abnormalities experienced faster gait speed decline (0.02 m/s per year) than those with no MRI abnormalities (0.01 m/s per year). Further adjustment for incident stroke, incident dementia, and 3MS score did not substantially attenuate hazard ratios for incident self-reported physical impairment or coefficients for decline in gait speed.

CONCLUSION: Subclinical structural brain abnormalities in high-functioning older adults can increase the risk of developing physical disabilities and declining in motor performance.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Brain, Female, Follow-Up Studies, Gait, Humans, Incidence, Magnetic Resonance Imaging, Male, Proportional Hazards Models, Psychomotor Disorders, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.53214.x}, author = {Rosano, Caterina and Kuller, Lewis H and Chung, Hyoju and Arnold, Alice M and Longstreth, William T and Newman, Anne B} } @article {878, title = {10-year follow-up of subclinical cardiovascular disease and risk of coronary heart disease in the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Jan 09}, pages = {71-8}, abstract = {

BACKGROUND: The incidence of coronary heart disease (CHD) is very high among individuals 65 years or older.

METHODS: We evaluated the relationships between measurements of subclinical disease at baseline (1989-1990) and at the third-year follow-up examination (1992-1993) and subsequent incidence of cardiovascular disease and total mortality as of June 2001. Approximately 61\% of the participants without clinical cardiovascular disease at baseline had subclinical disease based on our previously described criteria from the Cardiovascular Health Study.

RESULTS: The incidence of CHD was substantially increased for participants with subclinical disease compared with those who had no subclinical disease: 30.5 per 1000 person-years with and 16.3 per 1000 person-years without for white individuals, and 31.2 per 1000 person-years with and 12.5 per 1000 person-years without for black individuals. The risk persisted over the entire follow-up period. Incidence rates were higher for men than for women with or without subclinical disease, but there was little difference in rates for black individuals and white individuals.

CONCLUSIONS: In multivariable models, subclinical disease at baseline remained a significant predictor of CHD in both men and women; the hazard ratios (95\% confidence intervals) of their relative risks were 1.64 (1.30-2.06) and 1.49 (1.21-1.84), respectively. The presence of subclinical disease substantially increased the risk of subsequent CHD for participants with hypertension, diabetes mellitus, or elevated C-reactive protein. In summary, subclinical disease is very prevalent among older individuals, is independently associated with risk of CHD even over a 10-year follow-up period, and substantially increases the risk of CHD among participants with hypertension or diabetes mellitus.

}, keywords = {African Continental Ancestry Group, Aged, Blood Chemical Analysis, Cardiovascular Diseases, Comorbidity, Coronary Disease, Echocardiography, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Multivariate Analysis, Prevalence, Proportional Hazards Models, Regression Analysis, Risk Factors, Sex Distribution, United States}, issn = {0003-9926}, doi = {10.1001/archinte.166.1.71}, author = {Kuller, Lewis H and Arnold, Alice M and Psaty, Bruce M and Robbins, John A and O{\textquoteright}Leary, Daniel H and Tracy, Russell P and Burke, Gregory L and Manolio, Teri A and Chaves, Paolo H M} } @article {881, title = {Alcohol consumption and risk of coronary heart disease in older adults: the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Jan}, pages = {30-7}, abstract = {

OBJECTIVES: To evaluate several aspects of the relationship between alcohol use and coronary heart disease in older adults, including beverage type, mediating factors, and type of outcome.

DESIGN: Prospective cohort study.

SETTING: Four U.S. communities.

PARTICIPANTS: Four thousand four hundred ten adults aged 65 and older free of cardiovascular disease at baseline.

MEASUREMENTS: Risk of incident myocardial infarction or coronary death according to self-reported consumption of beer, wine, and spirits ascertained yearly.

RESULTS: During an average follow-up period of 9.2 years, 675 cases of incident myocardial infarction or coronary death occurred. Compared with long-term abstainers, multivariate relative risks of 0.90 (95\% confidence interval (CI)=0.71-1.14), 0.93 (95\% CI=0.73-1.20), 0.76 (95\% CI=0.53-1.10), and 0.58 (95\% CI=0.39-0.86) were found in consumers of less than one, one to six, seven to 13, and 14 or more drinks per week, respectively (P for trend=.007). Associations were similar for secondary coronary outcomes, including nonfatal and fatal events. No strong mediators of the association were identified, although fibrinogen appeared to account for 9\% to 10\% of the relationship. The associations were statistically similar for intake of wine, beer, and liquor and generally similar in subgroups, including those with and without an apolipoprotein E4 allele.

CONCLUSION: In this population, consumption of 14 or more drinks per week was associated with the lowest risk of coronary heart disease, although clinicians should not recommend moderate drinking to prevent coronary heart disease based on this evidence alone, because current National Institute on Alcohol Abuse and Alcoholism guidelines suggest that older adults limit alcohol intake to one drink per day.

}, keywords = {Aged, Alcohol Drinking, Apolipoproteins E, Beer, Cohort Studies, Coronary Disease, Female, Genotype, Health Behavior, Humans, Incidence, Male, Residence Characteristics, Risk Assessment, Socioeconomic Factors, United States, Wine}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2005.00561.x}, author = {Mukamal, Kenneth J and Chung, Hyoju and Jenny, Nancy S and Kuller, Lewis H and Longstreth, W T and Mittleman, Murray A and Burke, Gregory L and Cushman, Mary and Psaty, Bruce M and Siscovick, David S} } @article {844, title = {Congestive heart failure incidence and prognosis: case identification using central adjudication versus hospital discharge diagnoses.}, journal = {Ann Epidemiol}, volume = {16}, year = {2006}, month = {2006 Feb}, pages = {115-22}, abstract = {

PURPOSE: We compared hospitalized congestive heart failure (CHF) incidence and prognosis estimates using hospital discharge diagnoses or central adjudication.

METHODS: We used the Cardiovascular Health Study (CHS), a population-based cohort study of 5888 elderly adults. A physician committee adjudicated potential CHF events, confirmed by signs, symptoms, clinical tests, and/or medical therapy. A CHF discharge diagnosis included any of these ICD-9 codes in any position: 428, 425, 398.91, 402.01, 402.11, 402.91, and 997.1. We constructed an inception cohort of 1209 hospitalized, nonfatal, incident CHF cases, identified by discharge diagnosis, adjudication, or both.

RESULTS: Incidence rates for hospitalized CHF were 24.6 per 1000 person-years using discharge diagnoses and 17.1 per 1000 person-years using central adjudication. Compared to the group identified as having CHF by both methods, the group with only a discharge diagnosis (hazard ratio=0.77, 95\% confidence interval=0.65-0.91) and the group with central adjudication only (hazard ratio=0.72, 95\% confidence interval=0.55-0.94) had lower mortality rates.

CONCLUSIONS: In the elderly, studies using only discharge diagnoses, as compared to central adjudication, may estimate higher rates of incident hospitalized CHF. Mortality following CHF onset may be similar for these methods and higher if both methods are used together.

}, keywords = {Aged, Aged, 80 and over, Cohort Studies, Female, Heart Failure, Humans, Incidence, Male, Patient Discharge, Prognosis}, issn = {1047-2797}, doi = {10.1016/j.annepidem.2005.02.012}, author = {Schellenbaum, Gina D and Heckbert, Susan R and Smith, Nicholas L and Rea, Thomas D and Lumley, Thomas and Kitzman, Dalane W and Roger, Veronique L and Taylor, Herman A and Psaty, Bruce M} } @article {879, title = {Costs for heart failure with normal vs reduced ejection fraction.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Jan 09}, pages = {112-8}, abstract = {

BACKGROUND: Among the elderly population, heart failure (HF) with normal ejection fraction (EF) is more common than classic HF with low EF. However, there are few data regarding the costs of HF with normal EF. In a prospective, population-based cohort of elderly participants, we compared the costs and resource use of patients with HF and normal and reduced EF.

METHODS: A total of 4549 participants (84.5\% white; 40.6\% male) in the National Heart, Lung, and Blood Institute Cardiovascular Health Study were linked to Medicare claims from 1992 through 1998. By protocol echo examinations or clinical EF assessments, 881 participants with HF were characterized as having abnormal or normal EF. We applied semiparametric estimators to calculate mean costs per subject for a 5-year period.

RESULTS: There were 495 HF participants with normal EF (186 prevalent at study entry and 309 incident during the study period) and 386 participants with abnormal EF (166 prevalent and 220 incident). Participants with abnormal EF had more cardiology encounters and cardiac procedures. However, compared with abnormal EF participants, the 5-year costs for normal EF participants were similar in both the prevalent ($33,023 with abnormal EF and $32,580 with normal EF; P=.93) and incident ($49,128 with abnormal EF and $45,604 with normal EF; P=.55) groups. In models accounting for comorbid conditions, the costs with normal and abnormal EF remained similar.

CONCLUSIONS: Over a 5-year period, patients with HF and normal EF consume as many health care resources as those with reduced EF. These data highlight the substantial financial burden of HF with normal EF among the elderly population.

}, keywords = {Aged, Aged, 80 and over, Comorbidity, Echocardiography, Health Care Costs, Heart Failure, Humans, Incidence, Medicare, Prevalence, Prospective Studies, Regression Analysis, Statistics, Nonparametric, Stroke Volume, Systole, United States, Ventricular Function, Left}, issn = {0003-9926}, doi = {10.1001/archinte.166.1.112}, author = {Liao, Lawrence and Jollis, James G and Anstrom, Kevin J and Whellan, David J and Kitzman, Dalane W and Aurigemma, Gerard P and Mark, Daniel B and Schulman, Kevin A and Gottdiener, John S} } @article {899, title = {Education, cognitive test scores, and black-white differences in dementia risk.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Jun}, pages = {898-905}, abstract = {

OBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups.

DESIGN: Longitudinal, 6-year follow-up.

PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study.

MEASUREMENTS: Age, education (>10 years vs < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes.

RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95\% confidence interval (CI)=1.5-2.4 and 95\% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95\% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95\% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95\% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE.

CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.

}, keywords = {African Continental Ancestry Group, Aged, Cognition, Dementia, Educational Status, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Psychological Tests, Retrospective Studies, Risk Factors, United States}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2006.00747.x}, author = {Shadlen, Marie-Florence and Siscovick, David and Fitzpatrick, Annette L and Dulberg, Corinne and Kuller, Lewis H and Jackson, Sharon} } @article {900, title = {Factors associated with geographic variations in stroke incidence among older populations in four US communities.}, journal = {Stroke}, volume = {37}, year = {2006}, month = {2006 Aug}, pages = {1980-5}, abstract = {

BACKGROUND AND PURPOSE: In the Cardiovascular Health Study (CHS), we previously observed lower stroke incidence in Allegheny County, PA compared with the other 3 study sites. The purpose of this study was to study possible reasons for the lower stroke incidence in Allegheny County.

METHODS: CHS participants 65 years or older who were stroke-free at baseline (n=5639) were followed between 1989 to 1990 and 2000 for the development of stroke. Risk factors at baseline and their subsequent control were compared among both groups. Site-specific hazard ratios for stroke incidence were calculated using Cox regression models.

RESULTS: The unadjusted hazard ratio for total stroke incidence in Forsyth County, NC; Sacramento County, CA; and Washington County, MD combined compared with Allegheny County, PA was 1.74 (95\% CI: 1.42, 2.14). After adjustment for age and other traditional risk factors, there was modest reduction of the excess hazard in non-Allegheny sites compared with Allegheny County (hazard ratio=1.52, 95\% CI: 1.17, 1.98). Between baseline and the seventh-year visits, control of hypertension, diabetes, lipids, smoking, atrial fibrillation and transient ischemic attack were similar across sites. White matter grade > or = 3 on the baseline brain MRI was less common in Allegheny County (25.8\% versus 36.3\%, respectively; P<0.001) and accounted for 25\% of the excess hazard in non-Allegheny sites compared with Allegheny County.

CONCLUSIONS: Site differences in stroke risk factors at baseline and subsequent control only partially explain site differences in stroke incidence. White matter grade as a possible integrated measure of exposure and control of risk factors may help in explaining geographic variations in stroke incidence.

}, keywords = {Aged, Brain, California, Female, Humans, Incidence, Magnetic Resonance Imaging, Male, Maryland, North Carolina, Pennsylvania, Proportional Hazards Models, Risk Assessment, Risk Factors, Stroke}, issn = {1524-4628}, doi = {10.1161/01.STR.0000231454.77745.d9}, author = {El-Saed, Aiman and Kuller, Lewis H and Newman, Anne B and Lopez, Oscar and Costantino, Joseph and McTigue, Kathleen and Cushman, Mary and Kronmal, Richard} } @article {901, title = {Geographic variations in stroke incidence and mortality among older populations in four US communities.}, journal = {Stroke}, volume = {37}, year = {2006}, month = {2006 Aug}, pages = {1975-9}, abstract = {

BACKGROUND AND PURPOSE: Stroke is a leading cause of death and disability in the US. There is limited data on geographic variations in stroke incidence among older US populations who experience the majority of stroke burden. The purpose of this study was to compare stroke incidence and mortality rates in 4 US communities.

METHODS: Participants in the Cardiovascular Health Study (CHS) who had no history of stroke at baseline (n=5639) were followed for 10 or 7 years in predominantly white (n=5002) and black (n=637) participants, respectively. Incident stroke was validated by a stroke adjudication committee after ascertainment at annual visits, interim telephone contacts, and review of Medicare hospitalization data.

RESULTS: The 2000 US population age and sex standardized total stroke incidence rate for all CHS participants was 17.7 per 1000 person-years (95\% CI: 15.9, 19.5). The rate was significantly lower in Allegheny County, Pennsylvania 9.6/1000 person-years (95\% CI: 7.7, 11.5) than Forsyth County, North Carolina 19.2/1000 person-years (95\% CI: 15.6, 22.8), Sacramento County, California 20.7/1000 person-years (95\% CI: 16.9, 24.5), and Washington County, Maryland 19.8/1000 person-years (95\% CI: 16.1, 23.5). The lower stroke incidence rate in Allegheny County was consistent in gender, race, and age groups. Though not statistically significant, stroke mortality was also lower in Allegheny County than other 3 sites. The 1-month case fatality rate was similar in the 4 sites for all strokes, and by stroke types.

CONCLUSIONS: Understanding geographic variations in stroke incidence may be an important step in improving preventive practices of stroke.

}, keywords = {Aged, Aged, 80 and over, California, Female, Humans, Incidence, Male, Maryland, North Carolina, Pennsylvania, Stroke}, issn = {1524-4628}, doi = {10.1161/01.STR.0000231453.98473.67}, author = {El-Saed, Aiman and Kuller, Lewis H and Newman, Anne B and Lopez, Oscar and Costantino, Joseph and McTigue, Kathleen and Cushman, Mary and Kronmal, Richard} } @article {918, title = {Metabolic syndrome and cardiovascular disease in older people: The cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {54}, year = {2006}, month = {2006 Sep}, pages = {1317-24}, abstract = {

OBJECTIVES: To assess the prospective association between metabolic syndrome (MetS) and cardiovascular disease (CVD) in older people and to evaluate the effect of lowering the threshold for impaired fasting glucose (IFG) on the prevalence of IFG and MetS and the risk of CVD.

DESIGN: Prospective cohort study.

SETTING: Four field centers in U.S. communities.

PARTICIPANTS: Three thousand five hundred eighty-five subjects in the Cardiovascular Health Study free of diabetes mellitus and CVD at baseline (mean age 72, 62\% female, 14\% black).

MEASUREMENTS: Baseline measures of MetS components and adjudicated incident CVD events. MetS (2001) was defined first using the original criteria from the Third Adult Treatment Panel Report of the National Cholesterol Education Program (> or =3 of the following: large waist circumference (women >88 cm, men >102 cm), elevated triglycerides (> or =1.70 mmol/L), low high-density lipoprotein cholesterol (men <1.04 mmol/L, women <1.30 mmol/L), elevated fasting glucose (6.1-6.9 mmol/L), and high blood pressure (> or =130/85 mmHg or self-reported use of medications for hypertension). Subjects were also classified according to the revised definition of the MetS (2005) that applies the lower threshold for fasting glucose (5.6-6.9 mmol/L).

RESULTS: During follow-up (median 11 years), 818 coronary heart disease (CHD), 401 stroke, and 554 congestive heart failure (CHF) events occurred. Age- and race-adjusted hazard ratios (HRs) for CHD, stroke, and CHF were 1.30 (95\% confidence interval (CI) = 1.07-1.57), 0.94 (95\% CI = 0.73-1.21), and 1.40 (95\% CI = 1.12-1.76) for women and 1.35 (95\% CI = 1.10-1.66), 1.51 (95\% CI = 1.08-2.12), and 1.47 (95\% CI = 1.14-1.90) for men, respectively. Overall, women and men with MetS (2005) were 20\% to 30\% more likely to experience any CVD event than subjects without MetS (2005). Using the lower cut-point for IFG resulted in a near tripling in IFG prevalence (16\% to 46\%) and an additional 9\% classified with MetS (2005) but HRs similar to those estimated from the original MetS (2001) criteria. High blood pressure was the component most strongly associated with incident CHD.

CONCLUSION: Results from this study of an elderly, population-based cohort provide support for earlier investigations in primarily middle-aged populations that link the presence of MetS with the development of CVD and further underscore the importance of recognizing and treating its individual components, particularly high blood pressure.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Blood Glucose, Cardiovascular Diseases, Cohort Studies, European Continental Ancestry Group, Fasting, Female, Humans, Incidence, Male, Metabolic Syndrome, Risk Factors, Sex Factors}, issn = {0002-8614}, doi = {10.1111/j.1532-5415.2006.00862.x}, author = {McNeill, Ann Marie and Katz, Ronit and Girman, Cynthia J and Rosamond, Wayne D and Wagenknecht, Lynne E and Barzilay, Joshua I and Tracy, Russell P and Savage, Peter J and Jackson, Sharon A} } @article {919, title = {Progression of atherosclerotic renovascular disease: A prospective population-based study.}, journal = {J Vasc Surg}, volume = {44}, year = {2006}, month = {2006 Nov}, pages = {955-62; discussion 962-3}, abstract = {

OBJECTIVE: Previous reports from select hypertensive patients suggest that atherosclerotic renovascular disease (RVD) is rapidly progressive and associated with a decline in kidney size and kidney function. This prospective, population-based study estimates the incidence of new RVD and progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS).

METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women aged >65 years old. From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS) to define the presence or absence of significant RVD. Between 2002 and 2005, a second RDS study was performed in 119 participants (mean study interval, 8.0 +/- 0.8 years). Significant RVD was defined as hemodynamically significant stenosis (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery occlusion. Prevalent RVD was significant RVD at the first RDS, and incident disease was defined as new significant RVD at the second RDS. Significant change of RVD was defined as a change in RA-PSV of greater than two times the standard deviation of expected change over time, regardless of hemodynamic significance or progression to renal artery occlusion.

RESULTS: The second RDS study cohort included 119 CHS participants with 235 kidneys (35\% men; mean age, 82.8 +/- 3.4). On follow-up, no prevalent RVD (n = 13 kidneys; 6.0\%) progressed to occlusion. Twenty-nine kidneys without RVD at the first RDS demonstrated significant change in PSV at the second RDS; including nine kidneys with new significant RVD (8 new stenoses; 1 new occlusion). Controlling for within-subject correlation, the overall estimated change in RVD among all 235 kidneys was 14.0\% (95\% confidence interval [CI], 9.2\% to 21.4\%), with progression to significant RVD in 4.0\% (95\% CI, 1.9\% to 8.2\%). Longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression to new (ie, incident) significant RVD but not prevalent RVD.

CONCLUSIONS: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. In contrast to previous reports among select hypertensive patients, CHS participants with a low rate of clinical hypertension demonstrated a significant change of RVD in only 14.0\% of kidneys on follow-up of 8 years (annualized rate, 1.3\% per year). Progression to significant RVD was observed in only 4.0\% (annualized rate, 0.5\% per year), and no prevalent RVD progressed to occlusion.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Blood Flow Velocity, Blood Pressure, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Male, North Carolina, Population Surveillance, Prognosis, Prospective Studies, Renal Artery Obstruction, Severity of Illness Index, Time Factors, Ultrasonography, Doppler, Duplex}, issn = {0741-5214}, doi = {10.1016/j.jvs.2006.07.031}, author = {Pearce, Jeffrey D and Craven, Brandon L and Craven, Timothy E and Piercy, K Todd and Stafford, Jeanette M and Edwards, Matthew S and Hansen, Kimberley J} } @article {929, title = {Quantitative retinal venular caliber and risk of cardiovascular disease in older persons: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {166}, year = {2006}, month = {2006 Nov 27}, pages = {2388-94}, abstract = {

BACKGROUND: Small vessel disease may contribute to the risk of cardiovascular disease in older persons. We describe the relation of retinal vascular caliber to incident coronary heart disease (CHD) and stroke in elderly persons.

METHODS: Prospective population-based cohort study composed of 1992 men and women aged 69 to 97 years living in 4 US communities. Retinal arteriolar and venular calibers were measured from retinal photographs using a computer-assisted method. Incident CHD and stroke events were ascertained using standardized methods.

RESULTS: After 5 years of follow-up, there were 115 incident CHD events and 113 incident stroke events. Participants with larger retinal venular caliber had a higher incidence of CHD (11.7\%; 95\% confidence interval [CI], 8.7\%-15.8\%, vs 8.1\%; 95\% CI, 5.7\%-11.6\%), comparing largest with smallest venular caliber quartiles, and stroke (8.4\%; 95\% CI, 6.0-11.7, vs 5.8\%; 95\% CI, 3.9-8.4). At multivariable analysis, controlling for age, sex, race, arteriolar caliber, systolic and diastolic blood pressure, diabetes, glucose concentration, cigarette smoking, pack-years of smoking, and high-density-lipoprotein and low-density lipoprotein cholesterol levels, larger retinal venular caliber was associated with incident CHD (rate ratio, 3.0; 95\% CI, 1.6-5.7, comparing largest with smallest venular caliber quartiles; P(trend) = .001) and incident stroke (rate ratio, 2.2; 95\% CI, 1.1-4.3; P(trend) = .02). Additional adjustment for C-reactive protein and common and internal carotid artery intimal-media thickness had minimal effect on these associations. At multivariable analysis, smaller retinal arteriolar caliber was associated with incident CHD (rate ratio, 2.0; 95\% CI, 1.1-3.7, comparing largest with smallest arteriolar caliber quartiles; P = .03) but not stroke (rate ratio,1.1; 95\% CI, 0.5-2.2; P = .73).

CONCLUSION: Larger retinal venular caliber is independently associated with risk of cardiovascular disease in elderly persons.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Cardiovascular Diseases, Cohort Studies, Female, Humans, Image Processing, Computer-Assisted, Incidence, Male, Photography, Prospective Studies, Retinal Diseases, Retinal Vein, Retinal Vessels, Risk Factors, Stroke, United States}, issn = {0003-9926}, doi = {10.1001/archinte.166.21.2388}, author = {Wong, Tien Yin and Kamineni, Aruna and Klein, Ronald and Sharrett, A Richey and Klein, Barbara E and Siscovick, David S and Cushman, Mary and Duncan, Bruce B} } @article {880, title = {Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.}, journal = {J Thromb Haemost}, volume = {4}, year = {2006}, month = {2006 Jan}, pages = {107-13}, abstract = {

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression.

OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study.

METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up.

RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95\% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events.

CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

}, keywords = {Aged, Aged, 80 and over, Angina Pectoris, Biomarkers, Cardiovascular Diseases, Female, Humans, Incidence, Intercellular Adhesion Molecule-1, Male, Mortality, Myocardial Infarction, Regression Analysis, Risk Factors, Sex Factors, Solubility, Stroke}, issn = {1538-7933}, doi = {10.1111/j.1538-7836.2005.01678.x}, author = {Jenny, N S and Arnold, A M and Kuller, L H and Sharrett, A R and Fried, L P and Psaty, B M and Tracy, R P} } @article {939, title = {Alcohol consumption and risk and prognosis of atrial fibrillation among older adults: the Cardiovascular Health Study.}, journal = {Am Heart J}, volume = {153}, year = {2007}, month = {2007 Feb}, pages = {260-6}, abstract = {

BACKGROUND: The relationship of alcohol consumption with risk of atrial fibrillation (AF) is inconsistent in previous studies, and its relationship with prognosis of AF is undetermined.

METHODS: As part of the Cardiovascular Health Study, a population-based cohort of adults 65 years and older from 4 US communities, 5609 participants reported their use of beer, wine, and spirits yearly. We identified cases of AF with routine study electrocardiograms and validated discharge diagnoses from hospitalizations.

RESULTS: A total of 1232 cases of AF were documented during a mean of 9.1 years of follow-up. Compared with long-term abstainers, the multivariable-adjusted hazard ratios were 1.25 (95\% CI, 1.02-1.54) among former drinkers, 1.09 (95\% CI, 0.94-1.28) among consumers of less than 1 drink per week, 1.00 (95\% CI, 0.84-1.19) among consumers of 1 to 6 drinks per week, 1.06 (95\% CI, 0.82-1.37) among consumers of 7 to 13 drinks per week, and 1.09 (95\% CI, 0.88-1.37) among consumers of 14 or more drinks per week (P trend = 0.64). In analyses of mortality among participants with AF, the hazard ratios were 1.27 (95\% CI, 1.06-1.52) among former drinkers, 0.94 (95\% CI, 0.76-1.18) among consumers of less than 1 drink per week, 0.98 (95\% CI, 0.78-1.23) among consumers of 1 to 6 drinks per week, 0.73 (95\% CI, 0.51-1.03) among consumers of 7 to 13 drinks per week, and 0.81 (95\% CI, 0.59-1.11) among consumers of 14 or more drinks per week (P trend = 0.12).

CONCLUSIONS: Current moderate alcohol consumption is not associated with risk of AF or with risk of death after diagnosis of AF, but former drinking identifies individuals at higher risk.

}, keywords = {Aged, Alcohol Drinking, Atrial Fibrillation, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Prognosis, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2006.10.039}, author = {Mukamal, Kenneth J and Psaty, Bruce M and Rautaharju, Pentti M and Furberg, Curt D and Kuller, Lewis H and Mittleman, Murray A and Gottdiener, John S and Siscovick, David S} } @article {971, title = {Alcohol consumption and type 2 diabetes among older adults: the Cardiovascular Health Study.}, journal = {Obesity (Silver Spring)}, volume = {15}, year = {2007}, month = {2007 Jul}, pages = {1758-65}, abstract = {

OBJECTIVE: The objective was to examine the role of total and beverage-specific alcohol consumption on the incidence of type 2 diabetes mellitus (DM) among elderly men and women.

RESEARCH METHODS AND PROCEDURES: We studied prospectively 4655 participants of the Cardiovascular Health Study who were free of DM at baseline. Alcohol consumption was obtained at baseline and during follow-up examinations. DM was defined using fasting glucose and/or use of hypoglycemic medications. We used Cox proportional hazard models to estimate adjusted relative risks of diabetes across alcohol categories.

RESULTS: During a mean follow-up of 6.3 years, 234 incident cases of DM were documented. Compared with never drinkers, hazard ratios [95\% confidence interval (CI)] for DM were 0.7 (0.3 to 1.4), 0.5 (0.3 to 0.9), 0.6 (0.4 to 1.1), and 0.8 (0.4 to 1.3) for former drinkers and current drinkers of <1, 1 to 6, and 7+ drinks per week, respectively, for men after adjustment for age, BMI, education, and smoking. Corresponding values for women were 1.2 (0.6 to 2.3), 0.7 (0.4 to 1.1), 0.6 (0.3 to 1.1), and 0.4 (0.2 to 1.0), respectively. A reduced risk of DM was observed with all types of beverage consumed. Similar findings were observed when we repeated the above analyses using simple or weighted cumulative alcohol update and covariates over time.

DISCUSSION: Light to moderate alcohol consumption was associated with a lower incidence of DM among elderly people, irrespective of the type of beverage consumed.

}, keywords = {Aged, Aged, 80 and over, Alcohol Drinking, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Medicare, Middle Aged, Risk, Smoking, Temperance, United States}, issn = {1930-7381}, doi = {10.1038/oby.2007.209}, author = {Djouss{\'e}, Luc and Biggs, Mary L and Mukamal, Kenneth J and Siscovick, David S} } @article {967, title = {Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health Study.}, journal = {Circulation}, volume = {116}, year = {2007}, month = {2007 Jul 03}, pages = {32-8}, abstract = {

BACKGROUND: Carotid atherosclerosis, measured as carotid intima-media thickness or as characteristics of plaques, has been linked to cardiovascular disease (CVD) and to C-reactive protein (CRP) levels. We investigated the relationship between carotid atherosclerosis and CRP and their joint roles in CVD prediction.

METHODS AND RESULTS: Of 5888 participants in the Cardiovascular Health Study, an observational study of adults aged > or = 65 years, 5020 without baseline CVD were included in the analysis. They were followed up for as long as 12 years for CVD incidence and all-cause mortality after baseline ultrasound and CRP measurement. When CRP was elevated (> 3 mg/L) among those with detectable atherosclerosis on ultrasound, there was a 72\% (95\% CI, 1.46 to 2.01) increased risk for CVD death and a 52\% (95\% CI, 1.37 to 1.68) increased risk for all-cause mortality. Elevated CRP in the absence of atherosclerosis did not increase CVD or all-cause mortality risk. The proportion of excess risk attributable to the interaction of high CRP and atherosclerosis was 54\% for CVD death and 79\% for all-cause mortality. Addition of CRP or carotid atherosclerosis to conventional risk factors modestly increased in the ability to predict CVD, as measured by the c statistic.

CONCLUSIONS: In older adults, elevated CRP was associated with increased risk for CVD and all-cause mortality only in those with detectable atherosclerosis based on carotid ultrasound. Despite the significant associations of CRP and carotid atherosclerosis with CVD, these measures modestly improve the prediction of CVD outcomes after one accounts for the conventional risk factors.

}, keywords = {African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Carotid Artery Diseases, Cohort Studies, Comorbidity, Diabetes Mellitus, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Hyperlipidemias, Hypertension, Incidence, Inflammation, Kaplan-Meier Estimate, Male, Mass Screening, Mortality, Myocardial Infarction, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, ROC Curve, Smoking, Stroke, Survival Analysis, Tunica Intima, Tunica Media, Ultrasonography, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.106.645606}, author = {Cao, Jie J and Arnold, Alice M and Manolio, Teri A and Polak, Joseph F and Psaty, Bruce M and Hirsch, Calvin H and Kuller, Lewis H and Cushman, Mary} } @article {947, title = {Incidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study.}, journal = {Arch Neurol}, volume = {64}, year = {2007}, month = {2007 Mar}, pages = {416-20}, abstract = {

OBJECTIVES: To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study.

DESIGN: Prospective epidemiological study.

SETTING: The Cardiovascular Health Study Cognition Study of Pittsburgh, Pa, was conducted from 2002 through 2003 to determine the incidence of dementia in participants classified as having MCI in 1998 and 1999. Subjects There were 136 subjects with MCI. Mild cognitive impairment was subclassified as MCI amnestic type and MCI multiple cognitive deficits type (MCI-MCDT); subjects with MCI-MCDT were also grouped based on the presence of a memory impairment. Subjects with MCI were classified as possible when there were comorbidities that could explain the subjects{\textquoteright} cognitive deficits and as probable when there were none. Main Outcome Measure Dementia.

RESULTS: The incidence of all dementias in the subjects with MCI was 147 per 1000 person-years (mean follow-up overall, 4.3 years). Of the 136 subjects with MCI, 69 (51\%) in 1998 through 1999 progressed to dementia (57 [83\%] to Alzheimer disease [AD]), but 25 (18\%) returned to normal. Of the 10 subjects with probable MCI amnestic type, 7 (70\%) progressed to dementia (all of them to AD) and none returned to normal, whereas 7 (41\%) of the 17 subjects with possible MCI amnestic type became demented (6 [86\%] to AD) and 3 (18\%) returned to normal. Of the 40 subjects with probable MCI-MCDT, 21 (52\%) progressed to dementia (17 [81\%] to AD) and 2 (5\%) returned to normal. Of the 69 subjects with possible MCI-MCDT, 34 (49\%) progressed to dementia (28 [82\%] to AD) and 20 (29\%) returned to normal. Among the subjects with probable MCI-MCDT, 15 (54\%) of 28 with and 6 (50\%) of 12 without memory deficits progressed to dementia.

CONCLUSIONS: Subjects with MCI are at high risk for dementia. The probable MCI diagnosis identified individuals in the earliest stages of dementia, usually AD, whereas the possible MCI diagnosis identified a more heterogeneous group. However, this latter group had only a slightly lower rate of conversion to dementia than the group with probable MCI, suggesting that even with comorbid conditions, there is a high likelihood of the presence of a progressive dementing disorder.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular System, Cognition Disorders, Dementia, Disease Progression, Female, Humans, Incidence, Male, Retrospective Studies}, issn = {0003-9942}, doi = {10.1001/archneur.64.3.416}, author = {Lopez, Oscar L and Kuller, Lewis H and Becker, James T and Dulberg, Corinne and Sweet, Robert A and Gach, H Michael and DeKosky, Steven T} } @article {964, title = {Individual and neighborhood socioeconomic status and progressive chronic kidney disease in an elderly population: The Cardiovascular Health Study.}, journal = {Soc Sci Med}, volume = {65}, year = {2007}, month = {2007 Aug}, pages = {809-21}, abstract = {

Few studies have focused on the association between socioeconomic status (SES) and progressive chronic kidney disease (pCKD) in an elderly population. We conducted a cohort study of 4735 Cardiovascular Health Study participants, ages 65 and older and living in 4 US communities, to examine the independent risk of pCKD associated with income, education and living in a low SES area. pCKD was defined as creatinine elevation 0.4 mg/dL (35 micromol/L) over a 4-7 year follow-up or CKD hospitalization. Area SES was characterized using measures of income, wealth, education and occupation for 1990 (corresponding to time of enrollment) US Census block groups of residence. Age and study site-adjusted incidence rates (per 1000 person years) of pCKD by quartiles of area-level SES score, income and education showed decreasing rates with increasing SES. Cox proportional hazards models showed that living in the lowest SES area quartile, as opposed to the highest, was associated with 50\% greater risk of pCKD, after adjusting for age, gender, study site, baseline creatinine, and individual-level SES. This increased risk and trend persisted after adjusting for lifestyle risk factors, diabetes and hypertension. We found no significant independent associations between pCKD and individual-level income or education (after adjusting for all other SES factors). As such, living in a low SES area is associated with greater risk of pCKD in an elderly US population.

}, keywords = {Age Factors, Aged, Cohort Studies, Female, Humans, Incidence, Kidney Failure, Chronic, Male, Proportional Hazards Models, Residence Characteristics, Risk Factors, Sex Factors, Social Class, United States}, issn = {0277-9536}, doi = {10.1016/j.socscimed.2007.04.011}, author = {Merkin, Sharon Stein and Diez Roux, Ana V and Coresh, Josef and Fried, Linda F and Jackson, Sharon A and Powe, Neil R} } @article {977, title = {Risk factors for intracerebral hemorrhage in a pooled prospective study.}, journal = {Stroke}, volume = {38}, year = {2007}, month = {2007 Oct}, pages = {2718-25}, abstract = {

BACKGROUND AND PURPOSE: Few prospective studies have reported risk factors for intracerebral hemorrhage (ICH), and results are inconsistent. We studied risk factors for ICH in a pooled cohort of the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS).

METHODS: The ARIC cohort was recruited in 1987 to 1989 and involves 15 792 men and women, aged 45 to 64 years at baseline, sampled from 4 US communities. The CHS cohort was recruited in 1989 to 1993 and involves 5888 men and women, aged 65 or over at baseline, sampled from 4 US communities. Baseline measurements included many potential vascular risk factors. The cohorts were followed for incident stroke events.

RESULTS: Over 263 489 person-years of follow-up, 135 incident ICH events occurred. In a multivariable model, age, African-American ethnicity (versus Whites), and hypertension were positively associated with incident ICH, whereas low-density lipoprotein cholesterol and triglycerides were inversely related to incident ICH. Participants with systolic blood pressure >or=160 mm Hg or diastolic blood pressure >/=110 mm Hg had 5.55 (95\% CI 3.07 to 10.0) times the rate of ICH as nonhypertensives. Sex, smoking, alcohol intake, body mass index, waist-to-hip ratio, waist circumference, and diabetes were not related to ICH.

CONCLUSIONS: In this pooled cohort the risk factors for ICH were older age, African-American ethnicity, hypertension, lower LDL-C, and lower triglycerides.

}, keywords = {African Americans, Age Distribution, Cerebral Hemorrhage, Cholesterol, LDL, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Prevalence, Prospective Studies, Risk Factors, Stroke, Triglycerides}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.487090}, author = {Sturgeon, Jared D and Folsom, Aaron R and Longstreth, W T and Shahar, Eyal and Rosamond, Wayne D and Cushman, Mary} } @article {963, title = {Socioeconomic position and incident mobility impairment in the Cardiovascular Health Study.}, journal = {BMC Geriatr}, volume = {7}, year = {2007}, month = {2007 May 10}, pages = {11}, abstract = {

BACKGROUND: We investigated if personal socioeconomic position (SEP) factors and neighborhood characteristics were associated with incident mobility impairment in the elderly.

METHODS: We used data from the Cardiovascular Health Study, a longitudinal, population-based examination of coronary heart disease and stroke among persons aged 65 and older in the United States.

RESULTS: Among 3,684 persons without baseline mobility impairment, lower baseline SEP was associated with increased risk of incident mobility disability during the 10-year follow-up period, although the strengths of these associations varied by socioeconomic indicator and race/sex group.

CONCLUSION: Among independent-living elderly, SEP affected development of mobility impairment into later life. Particular effort should be made to prevent or delay its onset among the elderly with low income, education, and/or who live in economically disadvantaged neighborhoods.

}, keywords = {Aged, Aged, 80 and over, Coronary Disease, Disabled Persons, Education, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Mobility Limitation, Residence Characteristics, Social Class, Stroke, United States}, issn = {1471-2318}, doi = {10.1186/1471-2318-7-11}, author = {Nordstrom, Cheryl K and Diez Roux, Ana V and Schulz, Richard and Haan, Mary N and Jackson, Sharon A and Balfour, Jennifer L} } @article {1017, title = {Abdominal aortic aneurysms, increasing infrarenal aortic diameter, and risk of total mortality and incident cardiovascular disease events: 10-year follow-up data from the Cardiovascular Health Study.}, journal = {Circulation}, volume = {117}, year = {2008}, month = {2008 Feb 26}, pages = {1010-7}, abstract = {

BACKGROUND: Long-term data describing small abdominal aortic aneurysms (AAAs) and increasing infrarenal aortic diameters and their relationship to future surgical repair, total mortality, and incident cardiovascular disease (CVD) events, particularly among women, are sparse.

METHODS AND RESULTS: In 1992 to 1993, 4734 Cardiovascular Health Study participants > or = 65 years old had an abdominal aortic ultrasound evaluation. Of those screened, 416 had an AAA (infrarenal aortic diameter > or = 3.0 cm or an infrarenal/suprarenal ratio > or = 1.2). By 2002, there were 56 surgical AAA repairs and 10 AAA-related deaths. A single ultrasound screening demonstrated that aneurysm dilation > or = 3 cm identified 68\% of all AAA repairs over the next 10 years and 6 of the 10 AAA-related deaths in 4\% of the total population and that a > or = 2.5-cm dilation identified 91\% of all AAA repairs and 9 of the 10 deaths in 10\% of the total population. With adjusted Cox proportional hazard models, AAAs were associated with a higher risk of total mortality (hazard ratio 1.44, 95\% confidence interval 1.25 to 1.66) and incident CVD events (hazard ratio 1.52, 95\% confidence interval 1.25 to 1.85). Compared with diameters < 2.0 cm, infrarenal aortic diameters 2.0 to < 3.0 cm were associated with increased risk of incident CVD events in women and total mortality in men.

CONCLUSIONS: This study suggests that a 1-time screening of the abdominal aorta can acceptably identify individuals with a clinically significant AAA. Infrarenal aortic diameters > 2.0 cm are associated with a significantly increased risk of future CVD events and total mortality.

}, keywords = {Aged, Aged, 80 and over, Aorta, Abdominal, Aortic Aneurysm, Abdominal, Cause of Death, Female, Follow-Up Studies, Humans, Incidence, Intermittent Claudication, Kidney, Male, Prospective Studies, Risk Factors, Sex Distribution, Ultrasonography}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.107.720219}, author = {Freiberg, Matthew S and Arnold, Alice M and Newman, Anne B and Edwards, Matthew S and Kraemer, Kevin L and Kuller, Lewis H} } @article {1032, title = {Albuminuria and dementia in the elderly: a community study.}, journal = {Am J Kidney Dis}, volume = {52}, year = {2008}, month = {2008 Aug}, pages = {216-26}, abstract = {

BACKGROUND: Dementia is associated with microvascular disease of the retina. In this study, we examine whether cognitive status (normal cognition, mild cognitive impairment, and dementia) is associated with albuminuria, a microvascular disorder of the kidney.

STUDY DESIGN: Cross-sectional analysis.

SETTING \& PARTICIPANTS: 2,316 participants from the Cardiovascular Health Cognition Study who underwent brain magnetic resonance imaging and testing for albuminuria.

PREDICTOR: Doubling of albuminuria.

OUTCOME: Dementia defined according to neuropsychological and clinical evaluation.

MEASUREMENTS: Multinomial logistic modeling was used to estimate odds ratios (ORs) and 95\% confidence intervals (CIs) of dementia and mild cognitive impairment with doubling of albuminuria compared with the odds with normal cognition.

RESULTS: 283 participants (12.2\%) had dementia, 344 (14.9\%) had mild cognitive impairment, and 1,689 (72.9\%) had normal cognition. Compared with participants with normal cognition, doubling of albuminuria was associated with increased odds of dementia (OR, 1.22; 95\% CI, 1.15 to 1.29). Adjustment for prevalent cardiovascular disease and cardiovascular risk factors, lipid levels, C-reactive protein level, estimated glomerular filtration rate, and apolipoprotein E-4 genotype attenuated this association, but it remained statistically significant (OR, 1.12; 95\% CI, 1.03 to 1.22). Mild cognitive impairment was associated with albuminuria on unadjusted analysis, but not with adjustment for other factors.

LIMITATIONS: Results are cross-sectional; causality cannot be imputed.

CONCLUSIONS: The odds of dementia increased in the presence of albuminuria. These findings suggest a role of shared susceptibility for microvascular disease in the brain and kidney in older adults.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Albuminuria, Brain, Cognition, Cross-Sectional Studies, Dementia, Female, Humans, Incidence, Magnetic Resonance Imaging, Male, Odds Ratio, Population Surveillance, Prognosis, Retrospective Studies, Risk Factors}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2007.12.044}, author = {Barzilay, Joshua I and Fitzpatrick, Annette L and Luchsinger, Jose and Yasar, Sevil and Bernick, Charles and Jenny, Nancy S and Kuller, Lewis H} } @article {1035, title = {High insulinlike growth factor binding protein 1 level predicts incident congestive heart failure in the elderly.}, journal = {Am Heart J}, volume = {155}, year = {2008}, month = {2008 Jun}, pages = {1006-12}, abstract = {

BACKGROUND: Low levels of insulinlike growth factor 1 (IGF-I) may influence the development of age-related cardiovascular diseases including congestive heart failure (CHF). Insulinlike growth factor binding protein 1 (IGFBP-1), which increases during catabolic states and inhibits anabolic IGF-I effects, is increased in patients with CHF and has been associated prospectively with increased mortality among older adults and survivors of myocardial infarction. We investigated the association between fasting plasma levels of IGF-I, IGFBP-1, IGFBP-3, and insulin and risk of incident CHF in the prospective Cardiovascular Health Study.

METHODS: From among 5,888 adults 65 years old and older in the Cardiovascular Health Study, we studied 566 incident CHF cases and 1,072 comparison subjects after exclusion of underweight individuals (body mass index <18.5 kg/m(2)) and insulin users. Hazard ratios (HRs) with 95\% CIs for CHF were estimated after adjustment for age, race, sex, hypertension, systolic blood pressure, lipid levels, left ventricular hypertrophy, coronary disease, C-reactive protein, health status, diabetes, and body mass index.

RESULTS: High baseline IGFBP-1 level was a significant predictor of CHF, independent of established CHF risk factors and inflammation markers. The HR per SD of IGFBP-1 was 1.22 (95\% CI 1.07-1.39, P < .01). Relative to the lowest IGFBP-1 tertile, the HR was 1.29 (95\% CI 0.96-1.74, P = .09) for the second IGFBP-1 tertile and 1.47 (95\% CI 1.06-2.04; P = .02) for the highest IGFBP-1 tertile (tertile cut points 19.5 and 35.8 ng/mL). Total IGF-I, IGFBP-3, or insulin levels had no association with CHF after adjustment for CHF risk factors.

CONCLUSIONS: High circulating IGFBP-1 level may be a CHF risk factor among older adults.

}, keywords = {Aged, Aged, 80 and over, Female, Heart Failure, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Predictive Value of Tests, Prospective Studies, Risk Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2007.12.031}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Cappola, Anne R and Xue, XiaoNan and Psaty, Bruce M} } @article {1040, title = {High-density lipoprotein cholesterol and venous thromboembolism in the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Blood}, volume = {112}, year = {2008}, month = {2008 Oct 01}, pages = {2675-80}, abstract = {

We determined prospectively the risk of venous thromboembolism (VTE) in relation to baseline high-density lipoprotein cholesterol (HDL-c) in 19 049 participants of the Longitudinal Investigation of Thromboembolism Etiology (LITE), which was composed of 14 490 participants of the Atherosclerosis Risk in Communities (ARIC) study and 4559 participants of the Cardiovascular Health Study (CHS). In addition, we determined the risk of VTE in relation to baseline subfractions of HDL (HDL(2) and HDL(3)) and apolipoprotein A-I (apoA-I) in 14 488 participants of the ARIC study. Age-adjusted incidence rates of VTE by HDL-c quartile ranged from 1.64 to 1.91 per 1000 person-years in men and 1.40 to 1.94 per 1000 person-years in women; however, there was no apparent trend of VTE incidence across HDL-c quartiles for either sex. The multivariate adjusted hazard ratios of VTE by HDL-c quartiles (with quartile 4 as the reference) were nonsignificant for both sexes and ranged between 0.91 and 0.99 for men and 0.78 and 1.22 for women. Results did not differ in separate evaluations of idiopathic and secondary VTE. In the ARIC study, there was no trend of VTE hazard ratios across quartiles of HDL(2), HDL(3), or apoA-I. Low HDL-c does not appear to be an important VTE risk factor.

}, keywords = {Aged, Apolipoprotein A-I, Cholesterol, HDL, Female, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Proportional Hazards Models, United States, Venous Thromboembolism}, issn = {1528-0020}, doi = {10.1182/blood-2008-05-157412}, author = {Chamberlain, Alanna M and Folsom, Aaron R and Heckbert, Susan R and Rosamond, Wayne D and Cushman, Mary} } @article {998, title = {NSAID use and dementia risk in the Cardiovascular Health Study: role of APOE and NSAID type.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 Jan 01}, pages = {17-24}, abstract = {

BACKGROUND: Epidemiologic and laboratory studies suggest that nonsteroidal antiinflammatory drugs (NSAIDs) reduce risk of Alzheimer disease (AD). We therefore investigated the association between use of NSAIDs, aspirin, and the non-NSAID analgesic acetaminophen with incidence of dementia and AD.

METHODS: Participants in the Cardiovascular Health Cognition Study included 3,229 individuals aged 65 or older, free of dementia at baseline, with information on medication use. We used Cox proportional hazards regression to estimate the association of medication use with incident all-cause dementia, AD, and vascular dementia (VaD). Additional analyses considered the NSAID-AD relationship as a function of age, presence of at least one epsilon 4 allele at APOE, race, and individual NSAIDs{\textquoteright} reported ability to reduce production of the amyloid-beta peptide variant A beta(42).

RESULTS: Use of NSAIDs was associated with a lower risk of dementia (adjusted hazard ratio or aHR 0.76, 95\% CI or CI 0.60-0.96) and, in particular, AD (aHR 0.63, CI 0.45-0.88), but not VaD (aHR 0.92, CI 0.65-1.28). No similar trends were observed with acetaminophen (aHR 0.99, CI 0.79-1.24). Closer examination suggested AD risk reduction with NSAIDs only in participants having an APOE epsilon 4 allele (aHR 0.34, CI 0.18-0.65; aHR for others 0.88, CI 0.59-1.32). There was no advantage in AD risk reduction with NSAIDs reported to selectively reduce A beta(42).

CONCLUSIONS: Results were consistent with previous cohort studies showing reduced risk of AD in NSAID users, but this association was found only in those with an APOE epsilon 4 allele, and there was no advantage for A beta(42)-lowering NSAIDs.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Apolipoproteins E, Cardiovascular System, Dementia, Female, Humans, Incidence, Male, Proportional Hazards Models, Prospective Studies, Risk Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000284596.95156.48}, author = {Szekely, C A and Breitner, J C S and Fitzpatrick, A L and Rea, T D and Psaty, B M and Kuller, L H and Zandi, P P} } @article {1045, title = {Physical activity and incidence of atrial fibrillation in older adults: the cardiovascular health study.}, journal = {Circulation}, volume = {118}, year = {2008}, month = {2008 Aug 19}, pages = {800-7}, abstract = {

BACKGROUND: Vigorous exertion and endurance training have been reported to increase atrial fibrillation (AF). Associations of habitual light or moderate activity with AF incidence have not been evaluated.

METHODS AND RESULTS: We prospectively investigated associations of leisure-time activity, exercise intensity, and walking habits, assessed at baseline and updated during follow-up visits, with incident AF, diagnosed by annual 12-lead ECGs and hospital discharge records, from 1989 to 2001 among 5446 adults > or =65 years of age in the Cardiovascular Health Study. During 47 280 person-years of follow-up, 1061 new AF cases occurred (incidence 22.4/1000 person-years). In multivariable-adjusted analyses, leisure-time activity was associated with lower AF incidence in a graded manner, with 25\% (hazard ratio [HR] 0.75, 95\% confidence interval [CI] 0.61 to 0.90), 22\% (HR 0.78, 95\% CI 0.65 to 0.95), and 36\% (HR 0.64, 95\% CI 0.52 to 0.79) lower risk in quintiles 3, 4, and 5 versus quintile 1 (P for trend <0.001). Exercise intensity had a U-shaped relationship with AF (quadratic P=0.02): Versus no exercise, AF incidence was lower with moderate-intensity exercise (HR 0.72, 95\% CI 0.58 to 0.89) but not with high-intensity exercise (HR 0.87, 95\% CI 0.64 to 1.19). Walking distance and pace were each associated with lower AF risk in a graded manner (P for trend <0.001); when we assessed the combined effects of distance and pace, individuals in quartiles 2, 3, and 4 had 25\% (HR 0.75, 95\% CI 0.56 to 0.99), 32\% (HR 0.68, 95\% CI 0.50 to 0.92), and 44\% (HR 0.56, 95\% CI 0.38 to 0.82) lower AF incidence than individuals in quartile 1. Findings appeared unrelated to confounding by comorbidity or indication. After evaluation of cut points of moderate leisure-time activity (approximately 600 kcal/week), walking distance (12 blocks per week), and pace (2 mph), 26\% of all new AF cases (95\% CI 7\% to 43\%) appeared attributable to absence of these activities.

CONCLUSIONS: Light to moderate physical activities, particularly leisure-time activity and walking, are associated with significantly lower AF incidence in older adults.

}, keywords = {Aged, Aged, 80 and over, Atrial Fibrillation, Exercise, Female, Humans, Incidence, Leisure Activities, Male, Motor Activity, Prospective Studies, Walking}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.108.785626}, author = {Mozaffarian, Dariush and Furberg, Curt D and Psaty, Bruce M and Siscovick, David} } @article {1025, title = {Plasma amyloid levels and the risk of AD in normal subjects in the Cardiovascular Health Study.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 May 06}, pages = {1664-71}, abstract = {

OBJECTIVES: To examine the association between incident Alzheimer disease (AD), and plasma A beta 1-40 and A beta 1-42 levels in normal and mild cognitive impairment (MCI) subjects in a subgroup of participants of the Cardiovascular Health Study Cognition Study.

METHODS: We determined the plasma A beta 1-40 and A beta 1-42 levels of 274 nondemented subjects (232 normals and 42 with MCI) in 1998-1999 and repeated the measurements in 2002-2003. The mean age of the subjects at baseline was 79.3 +/- 3.6 years. We examined the association between A beta levels and incident AD over the ensuing 4.5 years, controlling for age, cystatin C level (marker of glomerular function), apolipoprotein E-4 allele, Modified-Mini-Mental State Examination scores, and MRI-identified infarcts.

RESULTS: In an unadjusted prospective model in normal subjects, both A beta 1-40 and A beta 1-42 levels in 1998-1999 were associated with incident AD (n = 55) in 2002-2003 (longitudinal analysis). In the fully adjusted multivariate model, neither A beta 1-42 nor A beta 1-40 nor their ratio was associated with incident AD. However, adjustment had a very small effect on point estimates for A beta 1-42, from an odds ratio (OR) of 1.61 (p = 0.007) in the unadjusted model to an OR of 1.46 (p = 0.08) in the fully adjusted model. In 2002-2003 (cross-sectional analysis), only the unadjusted models showed that both peptides were associated with AD.

CONCLUSIONS: Plasma A beta levels are affected by age and by systemic and CNS vascular risk factors. After controlling for these conditions, A beta-40 and A beta 1-42 are weak predictors of conversion to Alzheimer disease (AD) in normal subjects and are only weakly associated with AD in cross-sectional analysis. Consequently, plasma levels of A beta do not seem to be useful biomarkers for AD.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Biomarkers, Brain, Cerebrovascular Disorders, Comorbidity, Cross-Sectional Studies, Cystatin C, Cystatins, Female, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Models, Statistical, Neuropsychological Tests, Peptide Fragments, Predictive Value of Tests, Prospective Studies, Reference Values, Risk Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000306696.82017.66}, author = {Lopez, O L and Kuller, L H and Mehta, P D and Becker, J T and Gach, H M and Sweet, R A and Chang, Y F and Tracy, R and DeKosky, S T} } @article {1041, title = {Subjective and objective sleep quality in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the sleep heart health study.}, journal = {Am J Kidney Dis}, volume = {52}, year = {2008}, month = {2008 Aug}, pages = {305-13}, abstract = {

BACKGROUND: Studies examining sleep in the hemodialysis (HD) population have largely lacked an adequate comparison group. It therefore is uncertain whether poor sleep quality in the HD population reflects age, chronic health conditions, or effects of conventional HD therapy.

STUDY DESIGN: Cross-sectional matched-group study.

SETTING \& PARTICIPANTS: Forty-six in-center HD patients were compared with 137 community participants participating in the Sleep Heart Health Study matched for age, sex, body mass index, and race.

PREDICTOR: HD patients compared with community-dwelling non-HD participants.

OUTCOMES \& MEASUREMENTS: Home unattended polysomnography was performed and scored by using similar protocols. Sleep habits and sleepiness were assessed by using the Sleep Habits Questionnaire and Epworth Sleepiness Scale.

RESULTS: Average age of study samples was 63 years, 72\% were white, and average body mass index was 28 +/- 5 kg/m(2). HD patients were significantly more likely than community participants to have short sleep (odds ratio, 3.27; 95\% confidence interval, 1.16 to 9.25) and decreased sleep efficiency (odds ratio, 5.5; 95\% confidence interval, 1.5 to 19.6). HD patients reported more difficulty getting back to sleep (odds ratio, 2.25; 95\% confidence interval, 1.11 to 4.60) and waking up too early (odds ratio, 2.39; 95\% confidence interval, 1.01 to 5.66). There was no association between polysomnography sleep time and self-reported sleep time (r = 0.09; P = 0.6) or between the Epworth Sleepiness Scale and severity of sleep apnea (r = 0.10; P = 0.5) in the HD population.

LIMITATIONS: The study was limited to participants older than 45 years.

CONCLUSIONS: Kidney failure treated with thrice-weekly HD is significantly associated with poor subjective and objective sleep quality.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cross-Sectional Studies, Disease Progression, Female, Follow-Up Studies, Heart Rate, Humans, Incidence, Kidney Failure, Chronic, Male, Middle Aged, Odds Ratio, Pennsylvania, Polysomnography, Prognosis, Renal Dialysis, Retrospective Studies, Risk Factors, Severity of Illness Index, Sleep, Sleep Apnea Syndromes, Surveys and Questionnaires}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2008.04.019}, author = {Unruh, Mark L and Sanders, Mark H and Redline, Susan and Piraino, Beth M and Umans, Jason G and Chami, Hassan and Budhiraja, Rohit and Punjabi, Naresh M and Buysse, Daniel and Newman, Anne B} } @article {1021, title = {Total insulinlike growth factor 1 and insulinlike growth factor binding protein levels, functional status, and mortality in older adults.}, journal = {J Am Geriatr Soc}, volume = {56}, year = {2008}, month = {2008 Apr}, pages = {652-60}, abstract = {

OBJECTIVES: To assess the association between total insulinlike growth factor (IGF)-1, IGF binding protein-1 (IGFBP-1), and IGFBP-3 levels and functioning and mortality in older adults.

DESIGN: Cohort study.

SETTING/PARTICIPANTS: One thousand one hundred twenty-two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study.

MEASUREMENTS: Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality.

RESULTS: Higher IGFBP-1 predicted worse handgrip strength (P-trend(T1-T3)<.01) and slower walking speed (P-trend(T1-T3)=.03), lower IGF-1 had a borderline significant association with worse handgrip strength (P-trend(T1-T3)=.06), and better grip strength was observed in the middle IGFBP-3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP-1 predicted greater mortality (P-trend(T1-T3)<.001, hazard ratio (HR)(T3vsT1)=1.48, 95\% confidence interval (CI)=1.15-1.90); this association was borderline significant after additional confounder adjustment (P-trend(T1-T3)=.05, HR(T3vsT1)=1.35, 95\% CI=0.98-1.87). High IGFBP-1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P-trend(T1-T3)=.04, HR(T3vsT1)=1.40, CI=1.01-1.94). Neither IGF-1 nor IGFBP-3 level predicted mortality or incident ADL difficulties.

CONCLUSION: In adults aged 65 and older, high IGFBP-1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF-1 and IGFBP-3 had little association with these outcomes.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Enzyme-Linked Immunosorbent Assay, Fasting, Female, Follow-Up Studies, Hand Strength, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Survival Rate, United States, Walking}, issn = {1532-5415}, doi = {10.1111/j.1532-5415.2007.01637.x}, author = {Kaplan, Robert C and McGinn, Aileen P and Pollak, Michael N and Kuller, Lewis and Strickler, Howard D and Rohan, Thomas E and Xue, XiaoNan and Kritchevsky, Stephen B and Newman, Anne B and Psaty, Bruce M} } @article {1111, title = {Age-related macular degeneration and risk of coronary heart disease and stroke: the Cardiovascular Health Study.}, journal = {Ophthalmology}, volume = {116}, year = {2009}, month = {2009 Oct}, pages = {1913-9}, abstract = {

PURPOSE: To examine the associations of age-related macular degeneration (AMD) with incident coronary heart disease (CHD) and stroke in the Cardiovascular Health Study.

DESIGN: Population-based prospective cohort study.

PARTICIPANTS: A total of 1786 white and African-American participants free of CHD or 2228 participants free of stroke, aged 69 to 97 years.

METHODS: AMD was evaluated from photographs taken in 1997 and 1998.

MAIN OUTCOME MEASURES: Incident CHD and stroke ascertained using standardized methods.

RESULTS: Of the 1786 persons free of CHD, 303 developed incident CHD over 7 years. Participants with early AMD (n = 277) had a higher cumulative incidence of CHD than participants without early AMD (25.8\% vs. 18.9\%, P = 0.001). By adjusting for age, gender, race, systolic and diastolic blood pressure, hypertension status, fasting glucose, triglyceride, low-density lipoprotein cholesterol, cigarette smoking, pack years of smoking, and C-reactive protein, the presence of early AMD was associated with an increased risk of incident CHD (hazard ratio 1.57; 95\% confidence interval, 1.17-2.22). Late AMD (n = 25) was not associated with incident CHD (hazard ratio 0.78; 95\% confidence interval, 0.25-2.48). Among 2228 persons at risk, 198 developed incident stroke; neither early nor late AMD was associated with incident stroke.

CONCLUSIONS: This study suggests persons with early AMD have a higher risk of CHD but not stroke in a population aged 69 to 97 years. This provides further support that AMD is associated with underlying systemic vascular disease.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Blood Pressure, Cholesterol, LDL, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Macular Degeneration, Male, Prospective Studies, Risk Factors, Sex Factors, Stroke, Triglycerides, United States}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2009.03.046}, author = {Sun, Cong and Klein, Ronald and Wong, Tien Y} } @article {1112, title = {Angiotensin-converting enzyme inhibitors and cognitive decline in older adults with hypertension: results from the Cardiovascular Health Study.}, journal = {Arch Intern Med}, volume = {169}, year = {2009}, month = {2009 Jul 13}, pages = {1195-202}, abstract = {

BACKGROUND: Hypertension (HTN) is a risk factor for dementia, and animal studies suggest that centrally active angiotensin-converting enzyme (ACE) inhibitors (those that cross the blood-brain barrier) may protect against dementia beyond HTN control.

METHODS: Participants in the Cardiovascular Health Study Cognition Substudy with treated HTN and no diagnosis of congestive heart failure (n = 1054; mean age, 75 years) were followed up for a median of 6 years to determine whether cumulative exposure to ACE inhibitors (as a class and by central activity), compared with other anti-HTN agents, was associated with a lower risk of incident dementia, cognitive decline (by Modified Mini-Mental State Examination [3MSE]), or incident disability in instrumental activities of daily living (IADLs).

RESULTS: Among 414 participants who were exposed to ACE inhibitors and 640 who were not, there were 158 cases of incident dementia. Compared with other anti-HTN drugs, there was no association between exposure to all ACE inhibitors and risk of dementia (hazard ratio [HR], 1.01; 95\% confidence interval [CI], 0.88-1.15), difference in 3MSE scores (-0.32 points per year; P = .15), or odds of disability in IADLs (odds ratio [OR], 1.06; 95\% CI, 0.99-1.14). Adjusted results were similar. However, centrally active ACE inhibitors were associated with 65\% less decline in 3MSE scores per year of exposure (P = .01), and noncentrally active ACE inhibitors were associated with a greater risk of incident dementia (adjusted HR, 1.20; 95\% CI, 1.00-1.43 per year of exposure) and greater odds of disability in IADLs (adjusted OR, 1.16; 95\% CI, 1.03-1.30 per year of exposure) compared with other anti-HTN drugs.

CONCLUSIONS: While ACE inhibitors as a class do not appear to be independently associated with dementia risk or cognitive decline in older hypertensive adults, there may be within-class differences in regard to these outcomes. These results should be confirmed with a randomized clinical trial of a centrally active ACE inhibitor in the prevention of cognitive decline and dementia.

}, keywords = {Aged, Angiotensin-Converting Enzyme Inhibitors, Blood-Brain Barrier, Cognition, Dementia, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Prospective Studies, Risk Factors}, issn = {1538-3679}, doi = {10.1001/archinternmed.2009.175}, author = {Sink, Kaycee M and Leng, Xiaoyan and Williamson, Jeff and Kritchevsky, Stephen B and Yaffe, Kristine and Kuller, Lewis and Yasar, Sevil and Atkinson, Hal and Robbins, Mike and Psaty, Bruce and Goff, David C} } @article {1118, title = {Depressed mood is not a risk factor for incident dementia in a community-based cohort.}, journal = {Am J Geriatr Psychiatry}, volume = {17}, year = {2009}, month = {2009 Aug}, pages = {653-63}, abstract = {

OBJECTIVES: To determine the relationship between depressed mood and the development of Alzheimer disease in cognitively normal individuals.

DESIGN: Longitudinal and observational.

SETTING: Community-based cohort study.

PARTICIPANTS: A total of 288 participants in the Cardiovascular Health Study-Cognition Study (mean age: 77.52, SD =3.65, range: 70-89). All of the participants were adjudicated as cognitively normal in 1998/1999, and all had at least three visits before 1998/1999 with measures of cognition and mood state. The mean length of follow-up from 1998-1999 to 2007 was 7.1 years (range: 1-9 years, median =9 years).

MEASUREMENTS: The Center for Epidemiological Studies-Depression Scale (CESD) was used to index mood state, and the Modified Mini-Mental State Examination (3MSE) was the index of cognitive function among participants before 1998/1999. These measures were considered in two ways: participants were classified according to: 1) whether they showed a high-negative correlation between their CESD and 3MSE scores (i.e., indicating that greater depression was linked to poorer cognition) and 2) whether they showed persistently elevated CESD scores. The study outcome, development of dementia (N = 48), was based on consensus classifications, which was based on detailed neuropsychological and neurological exams.

RESULTS: The authors could find no consistent relationship between mood state, either alone or in relation to cognitive status, and the subsequent development of dementia. Those individuals whose cognitive functions were highly correlated with their mood state were no more likely to develop dementia than other participants. Those who had persistently depressed mood were also no more likely to develop dementia than those without persistently depressed mood.

CONCLUSION: Within the confines of this prospective, community-based study of elderly adults, the authors could not find strong evidence to support the hypothesis that mood disturbance was linked with the development of dementia.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Dementia, Depression, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mental Status Schedule, Prospective Studies, Psychiatric Status Rating Scales, Residence Characteristics, Risk Factors}, issn = {1545-7214}, author = {Becker, James T and Chang, Yue-Fang and Lopez, Oscar L and Dew, Mary Amanda and Sweet, Robert A and Barnes, Deborah and Yaffe, Kristine and Young, Jeffrey and Kuller, Lewis and Reynolds, Charles F} } @article {1095, title = {Lifestyle risk factors and new-onset diabetes mellitus in older adults: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {169}, year = {2009}, month = {2009 Apr 27}, pages = {798-807}, abstract = {

BACKGROUND: The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established. The objective of this study was to determine how lifestyle factors, assessed in combination, relate to new-onset diabetes in a broad and relatively unselected population of older adults.

METHODS: We prospectively examined associations of lifestyle factors, measured using repeated assessments later in life, with incident diabetes mellitus during a 10-year period (1989-1998) among 4883 men and women 65 years or older (mean [SD] age at baseline, 73 [6] years) enrolled in the Cardiovascular Health Study. Low-risk lifestyle groups were defined by physical activity level (leisure-time activity and walking pace) above the median; dietary score (higher fiber intake and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean glycemic index) in the top 2 quintiles; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or moderate); body mass index less than 25 (calculated as weight in kilograms divided by height in meters squared); and waist circumference of 88 cm for women or 92 cm for men. The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications. We also evaluated fasting and 2-hour postchallenge glucose levels.

RESULTS: During 34,539 person-years, 337 new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years). After adjustment for age, sex, race, educational level, and annual income, each lifestyle factor was independently associated with incident diabetes. Overall, the rate of incident diabetes was 35\% lower (relative risk, 0.65; 95\% confidence interval, 0.59-0.71) for each 1 additional lifestyle factor in the low-risk group. Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82\% lower incidence of diabetes (relative risk, 0.18; 95\% confidence interval, 0.06-0.56) compared with all other participants. When absence of adiposity (either body mass index <25 or waist circumference < or =88/92 cm for women/men) was added to the other 4 low-risk lifestyle factors, incidence of diabetes was 89\% lower (relative risk, 0.11; 95\% confidence interval, 0.01-0.76). Overall, 9 of 10 new cases of diabetes appeared to be attributable to these 5 lifestyle factors. Associations were slightly attenuated, but still highly significant, for incident diabetes defined by medication use or glucose level.

CONCLUSION: Even later in life, combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus.

}, keywords = {Age of Onset, Aged, Aged, 80 and over, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Life Style, Male, National Heart, Lung, and Blood Institute (U.S.), Prospective Studies, Risk Factors, United States}, issn = {1538-3679}, doi = {10.1001/archinternmed.2009.21}, author = {Mozaffarian, Dariush and Kamineni, Aruna and Carnethon, Mercedes and Djouss{\'e}, Luc and Mukamal, Kenneth J and Siscovick, David} } @article {1135, title = {Lipoprotein-associated phospholipase A(2) and risk of congestive heart failure in older adults: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {2}, year = {2009}, month = {2009 Sep}, pages = {429-36}, abstract = {

BACKGROUND: Inflammation may be a causative factor in congestive heart failure (CHF). Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an inflammation marker associated with vascular risk. One previous study showed an association of Lp-PLA(2) activity with CHF risk, but there were only 94 CHF cases and Lp-PLA(2) antigen, which is available clinically in the United States, was not measured.

METHODS AND RESULTS: We measured baseline Lp-PLA(2) antigen and activity in 3991 men and women without baseline CHF or cardiovascular disease who were participating in the Cardiovascular Health Study, a prospective observational study of adults 65 years or older. Cox proportional hazards models adjusted for age, sex, clinic site, race, low-density and high-density lipoprotein cholesterol, body mass index, systolic and diastolic blood pressure, hypertension, smoking status, pack-years, and diabetes were used to calculate hazard ratios and 95\% CIs for incident CHF. Further models adjusted for coronary disease events during follow-up and C-reactive protein. Eight hundred twenty-nine participants developed CHF during 12.1 years. Adjusted hazard ratios for CHF with Lp-PLA(2) in the fourth compared with the first quartile were 1.44 (95\% CI, 1.16 to 1.79) for Lp-PLA(2) antigen and 1.06 (95\% CI, 0.84 to 1.32) for activity. Adjustment for incident coronary disease attenuated the hazard ratio for Lp-PLA(2) antigen to 1.26 (95\% CI, 1.02 to 1.57), adjustment for C-reactive protein had minimal impact.

CONCLUSIONS: Lp-PLA(2) antigen was associated with risk of future CHF in older people, independent of CHF and coronary risk factors, and partly mediated by coronary disease events. Further clinical and basic research is needed to better understand the role of Lp-PLA(2) in CHF.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Biomarkers, C-Reactive Protein, Female, Fibrinogen, Heart Failure, Humans, Incidence, Inflammation Mediators, Interleukin-6, Kaplan-Meier Estimate, Male, Population Surveillance, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.108.839613}, author = {Suzuki, Takeki and Solomon, Cam and Jenny, Nancy Swords and Tracy, Russell and Nelson, Jeanenne J and Psaty, Bruce M and Furberg, Curt and Cushman, Mary} } @article {1083, title = {Prospective study of sleep-disordered breathing and hypertension: the Sleep Heart Health Study.}, journal = {Am J Respir Crit Care Med}, volume = {179}, year = {2009}, month = {2009 Jun 15}, pages = {1159-64}, abstract = {

RATIONALE: Cross-sectional epidemiologic studies show an association between sleep-disordered breathing and hypertension, but only one cohort study has examined sleep-disordered breathing as a risk factor for incident hypertension.

OBJECTIVES: To examine whether sleep-disordered breathing increases the risk of incident hypertension among persons 40 years of age and older.

METHODS: In a prospective cohort study, we analyzed data from 2,470 participants who at baseline did not have hypertension, defined as blood pressure of at least 140/90 mm Hg or taking antihypertensive medication. The apnea-hypopnea index (AHI), the number of apneas plus hypopneas per hour of sleep, was measured by overnight in-home polysomnography. We estimated odds ratios for developing hypertension during 5 years of follow-up according to baseline AHI.

MEASUREMENTS AND MAIN RESULTS: The odds ratios for incident hypertension increased with increasing baseline AHI; however, this relationship was attenuated and not statistically significant after adjustment for baseline body-mass index. Although not statistically significant, the observed association between a baseline AHI greater than 30 and future hypertension (odds ratio, 1.51; 95\% confidence interval, 0.93-2.47) does not exclude the possibility of a modest association.

CONCLUSIONS: Among middle-aged and older persons without hypertension, much of the relationship between AHI and risk of incident hypertension was accounted for by obesity. After adjustment for body mass index, the AHI was not a significant predictor of future hypertension, although a modest influence of an AHI greater than 30 on hypertension could not be excluded.

}, keywords = {Adult, Blood Pressure, Confidence Intervals, Cross-Sectional Studies, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Male, Middle Aged, Odds Ratio, Polysomnography, Prognosis, Prospective Studies, Risk Factors, Sleep Apnea Syndromes, Time Factors, United States}, issn = {1535-4970}, doi = {10.1164/rccm.200712-1809OC}, author = {O{\textquoteright}Connor, George T and Caffo, Brian and Newman, Anne B and Quan, Stuart F and Rapoport, David M and Redline, Susan and Resnick, Helaine E and Samet, Jonathan and Shahar, Eyal} } @article {1090, title = {Race, gender, and mortality in adults > or =65 years of age with incident heart failure (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {103}, year = {2009}, month = {2009 Apr 15}, pages = {1120-7}, abstract = {

In patients with heart failure (HF), mortality is lower in women versus men. However, it is unknown whether the survival advantage in women compared with men is present in both whites and African Americans with HF. The inception cohort consisted of adults > or =65 years with incident HF after enrollment in the CHS, a prospective population-based study of cardiovascular disease. Of 5,888 CHS subjects, 1,264 developed new HF and were followed up for 3 years. Subjects were categorized into 4 race-gender groups, and Cox proportional hazard regression models were used to examine whether 3-year total and cardiovascular mortality differed among the 4 groups after adjusting for sociodemographic factors, co-morbidities, and treatment. A gender-race interaction was also tested for each outcome. In subjects with incident HF, African Americans had more hypertension and diabetes than whites, and white men had more coronary heart disease than other gender-race groups. Receipt of cardiovascular treatments among the 4 groups was similar. Mortality rates after HF were lower in women compared with men (for white women, African-American women, African-American men, and white men, total mortality was 35.5, 33.6, 44.4, and 40.5/100 person-years, and cardiovascular mortality was 18.4, 19.5, 20.2, and 22.7/100 person-years, respectively). After adjusting for covariates, women had a 15\% to 20\% lower risk of total and cardiovascular mortality compared with men, but there was no significant difference in outcome by race. The gender-race interaction for either outcome was not significant. In conclusion, in older adults with HF, women had significantly better survival than men irrespective of race, suggesting that gender-based survival differences may be more important than race-based differences.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Continental Population Groups, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Male, Proportional Hazards Models, Sex Factors, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2008.12.043}, author = {Parashar, Susmita and Katz, Ronit and Smith, Nicholas L and Arnold, Alice M and Vaccarino, Viola and Wenger, Nanette K and Gottdiener, John S} } @article {1121, title = {Replication of findings on the association of genetic variation in 24 hemostasis genes and risk of incident venous thrombosis.}, journal = {J Thromb Haemost}, volume = {7}, year = {2009}, month = {2009 Oct}, pages = {1743-6}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Female, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Haplotypes, Hemostasis, Humans, Incidence, Male, Menopause, Middle Aged, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk, Thrombophilia, Venous Thrombosis, Young Adult}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2009.03567.x}, author = {Smith, N L and Wiggins, K L and Reiner, A P and Lange, L A and Cushman, M and Heckbert, S R and Lumley, T and Rice, K M and Folsom, A R and Psaty, B M} } @article {1146, title = {Sibling history of myocardial infarction or stroke and risk of cardiovascular disease in the elderly: the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {19}, year = {2009}, month = {2009 Dec}, pages = {858-66}, abstract = {

PURPOSE: To assess the relationship between sibling history of myocardial infarction (MI) or stroke with cardiovascular disease (CVD) and risk factors in older adults.

METHODS: Prospective cohort study of 5,888 older adults participating in the Cardiovascular Health Study (CHS). History of MI and stroke in siblings was obtained by self-report. Participants with positive sibling histories were compared to those with negative histories to determine if prevalent or incident disease (coronary heart disease [CHD], MI, stroke, angina), subclinical CVD (carotid wall thickness, left ventricular mass, hypertension, diabetes, ankle-brachial index), CVD risk factors differed between groups.

RESULTS: More than 91\% (n = 5,383) of CHS participants reported at least one sibling. Sibling history of MI was associated with increased disease prevalence (CHD, MI, angina) and incidence (CHD, angina). Sibling history of stroke was associated with increased disease prevalence (CHD, angina). Sibling history of either MI or stroke was associated with increased disease prevalence and incidence for CHD, MI and angina, more subclinical disease, and a higher CVD risk profile.

CONCLUSIONS: Sibling history of MI and stroke were markers of higher CVD risk status even in older adults. Of clinical importance, participants with positive sibling history have numerous risk factors amenable to intervention.

}, keywords = {Aged, Atherosclerosis, Female, Genetic Predisposition to Disease, Humans, Incidence, Male, Myocardial Infarction, Odds Ratio, Prevalence, Prospective Studies, Risk Factors, Siblings, Stroke, United States}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2009.07.095}, author = {Yanez, N David and Burke, Gregory L and Manolio, Teri and Gardin, Julius M and Polak, Joseph} } @article {1102, title = {Spousal suffering and partner{\textquoteright}s depression and cardiovascular disease: the Cardiovascular Health Study.}, journal = {Am J Geriatr Psychiatry}, volume = {17}, year = {2009}, month = {2009 Mar}, pages = {246-54}, abstract = {

OBJECTIVES: To assess the effects of suffering in a spouse on prevalent and incident psychiatric (depression) and physical morbidity (cardiovascular disease [CVD]) in their partner, controlling for known risk factors for depression and CVD.

DESIGN: Descriptive longitudinal study.

PARTICIPANTS: A total of 1,330 older married couples enrolled in the Cardiovascular Health Study, a large epidemiologic study of the elderly.

MEASUREMENTS: Predictor variables were physical, psychological, and existential/spiritual indicators of suffering. Primary outcomes were prevalent and incident depression and CVD.

RESULTS: Controlling for known risk factors for depression, the authors found a dose-response relationship between suffering in a spouse and concurrent depression in their partner as well as a relationship between suffering and the partner{\textquoteright}s future risk for depression. With respect to CVD, and controlling for subclinical CVD at baseline, husbands whose wives reported high levels of suffering also had higher rates of prevalent CVD, but there were no significant associations between wives suffering and husbands incident CVD. There were no associations between husbands{\textquoteright} suffering and wives{\textquoteright} prevalent or incident CVD.

CONCLUSION: Exposure to spousal suffering is an independent and unique source of distress in married couples that contributes to psychiatric and physical morbidity. More attention should be paid to the interpersonal effects of suffering in married couples and to its role in contributing to morbidity.

}, keywords = {Activities of Daily Living, Aged, Cardiovascular Diseases, Caregivers, Depression, Female, Follow-Up Studies, Humans, Incidence, Logistic Models, Longitudinal Studies, Male, Prevalence, Risk Factors, Socioeconomic Factors, Spouses, Stress, Psychological, Surveys and Questionnaires}, issn = {1545-7214}, doi = {10.1097/JGP.0b013e318198775b}, author = {Schulz, Richard and Beach, Scott R and Hebert, Randy S and Martire, Lynn M and Monin, Joan K and Tompkins, Connie A and Albert, Steven M} } @article {1228, title = {Albuminuria and the risk of incident stroke and stroke types in older adults.}, journal = {Neurology}, volume = {75}, year = {2010}, month = {2010 Oct 12}, pages = {1343-50}, abstract = {

BACKGROUND: The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate.

METHODS: These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006.

RESULTS: A total of 390 participants had an incident stroke: 81\% ischemic, 12\% hemorrhagic, and 7\% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95\% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95\% CI 0.91-1.84) and for cystatin C was 1.22 (95\% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories.

CONCLUSIONS: UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Community Health Services, Confidence Intervals, Female, Geriatric Assessment, Glomerular Filtration Rate, Humans, Incidence, Longitudinal Studies, Male, Proportional Hazards Models, Retrospective Studies, Risk Factors, Stroke}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e3181f73638}, author = {Aguilar, M I and O{\textquoteright}Meara, E S and Seliger, S and Longstreth, W T and Hart, R G and Pergola, P E and Shlipak, M G and Katz, R and Sarnak, M J and Rifkin, D E} } @article {1210, title = {Association between adiposity in midlife and older age and risk of diabetes in older adults.}, journal = {JAMA}, volume = {303}, year = {2010}, month = {2010 Jun 23}, pages = {2504-12}, abstract = {

CONTEXT: Adiposity is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, but the relationship between body composition and type 2 diabetes is not well described among older adults.

OBJECTIVE: To examine the relationship between adiposity, changes in adiposity, and risk of incident type 2 diabetes in adults 65 years of age and older.

DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (1989-2007) of 4193 men and women 65 years of age and older in the Cardiovascular Health Study. Measures of adiposity were derived from anthropometry and bioelectrical impedance data at baseline and anthropometry repeated 3 years later.

MAIN OUTCOME MEASURE: Incident diabetes was ascertained based on use of antidiabetic medication or a fasting glucose level of 126 mg/dL or greater.

RESULTS: Over median follow-up of 12.4 years (range, 0.9-17.8 years), 339 cases of incident diabetes were ascertained (7.1/1000 person-years). The adjusted hazard ratio (HR) (95\% confidence interval [CI]) of type 2 diabetes for participants in the highest quintile of baseline measures compared with those in the lowest was 4.3 (95\% CI, 2.9-6.5) for body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), 3.0 (95\% CI, 2.0-4.3) for BMI at 50 years of age, 4.2 (95\% CI, 2.8-6.4) for weight, 4.0 (95\% CI, 2.6-6.0) for fat mass, 4.2 (95\% CI, 2.8-6.2) for waist circumference, 2.4 (95\% CI, 1.6-3.5) for waist-hip ratio, and 3.8 (95\% CI, 2.6-5.5) for waist-height ratio. However, when stratified by age, participants 75 years of age and older had HRs approximately half as large as those 65 to 74 years of age. Compared with weight-stable participants (+/-2 kg), those who gained the most weight from 50 years of age to baseline (> or = 9 kg), and from baseline to the third follow-up visit (> or = 6 kg), had HRs for type 2 diabetes of 2.8 (95\% CI, 1.9-4.3) and 2.0 (95\% CI, 1.1-3.7), respectively. Participants with a greater than 10-cm increase in waist size from baseline to the third follow-up visit had an HR of type 2 diabetes of 1.7 (95\% CI, 1.1-2.8) compared with those who gained or lost 2 cm or less.

CONCLUSION: Among older adults, overall and central adiposity, and weight gain during middle age and after the age of 65 years are associated with risk of diabetes.

}, keywords = {Adiposity, Age Factors, Aged, Body Mass Index, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Male, Prospective Studies, Risk Factors, United States, Weight Gain}, issn = {1538-3598}, doi = {10.1001/jama.2010.843}, author = {Biggs, Mary L and Mukamal, Kenneth J and Luchsinger, Jos{\'e} A and Ix, Joachim H and Carnethon, Mercedes R and Newman, Anne B and de Boer, Ian H and Strotmeyer, Elsa S and Mozaffarian, Dariush and Siscovick, David S} } @article {1197, title = {Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.}, journal = {Circ Cardiovasc Genet}, volume = {3}, year = {2010}, month = {2010 Jun}, pages = {256-66}, abstract = {

BACKGROUND: Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study.

METHODS AND RESULTS: Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12\%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16\%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3.

CONCLUSIONS: We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF.

}, keywords = {African Americans, Aged, Aged, 80 and over, Cohort Studies, Endopeptidases, European Continental Ancestry Group, Female, Genome-Wide Association Study, Heart Failure, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Ubiquitin-Specific Proteases}, issn = {1942-3268}, doi = {10.1161/CIRCGENETICS.109.895763}, author = {Smith, Nicholas L and Felix, Janine F and Morrison, Alanna C and Demissie, Serkalem and Glazer, Nicole L and Loehr, Laura R and Cupples, L Adrienne and Dehghan, Abbas and Lumley, Thomas and Rosamond, Wayne D and Lieb, Wolfgang and Rivadeneira, Fernando and Bis, Joshua C and Folsom, Aaron R and Benjamin, Emelia and Aulchenko, Yurii S and Haritunians, Talin and Couper, David and Murabito, Joanne and Wang, Ying A and Stricker, Bruno H and Gottdiener, John S and Chang, Patricia P and Wang, Thomas J and Rice, Kenneth M and Hofman, Albert and Heckbert, Susan R and Fox, Ervin R and O{\textquoteright}Donnell, Christopher J and Uitterlinden, Andr{\'e} G and Rotter, Jerome I and Willerson, James T and Levy, Daniel and van Duijn, Cornelia M and Psaty, Bruce M and Witteman, Jacqueline C M and Boerwinkle, Eric and Vasan, Ramachandran S} } @article {1245, title = {Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults.}, journal = {JAMA}, volume = {304}, year = {2010}, month = {2010 Dec 08}, pages = {2494-502}, abstract = {

CONTEXT: Older adults comprise the majority of new-onset heart failure (HF) diagnoses, but traditional risk-factor prediction models have limited accuracy in this population to identify those at highest risk for hospitalization or death.

OBJECTIVES: To determine if cardiac troponin T (cTnT) measured by a highly sensitive assay would be detectable in the majority of community-dwelling older adults, and if serial measures were associated with risk of HF hospitalization and cardiovascular death.

DESIGN, SETTING, AND PARTICIPANTS: A longitudinal nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling adults aged 65 years or older without prior HF who had cTnT measured using a highly sensitive assay at baseline (1989-1990) and repeated after 2 to 3 years (n = 2918).

MAIN OUTCOME MEASURES: New-onset HF and cardiovascular death were examined through June 2008 with respect to cTnT concentrations, accounting for clinical risk predictors.

RESULTS: Cardiac troponin T was detectable (>=3.00 pg/mL) in 2794 participants (66.2\%). During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and 1103 cardiovascular deaths occurred, with a greater risk of both end points associated with higher cTnT concentrations. Among those participants with the highest cTnT concentrations (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95\% confidence interval [CI], 5.8-7.2; adjusted hazard ratio [aHR], 2.48; 95\% CI, 2.04-3.00) for HF and an incidence rate of 4.8 (95\% CI, 4.3-5.4; aHR, 2.91; 95\% CI, 2.37-3.58) for cardiovascular death compared with participants with undetectable cTnT levels (incidence rate, 1.6; 95\% CI, 1.4-1.8 and 1.1; 95\% CI, 0.9-1.2 for HF and cardiovascular death, respectively). Among individuals with initially detectable cTnT, a subsequent increase of more than 50\% (n = 393, 22\%) was associated with a greater risk for HF (aHR, 1.61; 95\% CI, 1.32-1.97) and cardiovascular death (aHR, 1.65; 95\% CI, 1.35-2.03) and a decrease of more than 50\% (n = 247, 14\%) was associated with a lower risk for HF (aHR, 0.73; 95\% CI, 0.54-0.97) and cardiovascular death (aHR, 0.71; 95\% CI, 0.52-0.97) compared with participants with 50\% or less change. Addition of baseline cTnT measurements to clinical risk factors was associated with only modest improvement in discrimination, with change in C statistic of 0.015 for HF and 0.013 for cardiovascular death.

CONCLUSION: In this cohort of older adults without known HF, baseline cTnT levels and changes in cTnT levels measured with a highly sensitive assay were significantly associated with incident HF and cardiovascular death.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Heart Failure, Humans, Incidence, Male, Predictive Value of Tests, Risk, Sensitivity and Specificity, Troponin T, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1708}, author = {deFilippi, Christopher R and de Lemos, James A and Christenson, Robert H and Gottdiener, John S and Kop, Willem J and Zhan, Min and Seliger, Stephen L} } @article {1177, title = {Cystatin C and sudden cardiac death risk in the elderly.}, journal = {Circ Cardiovasc Qual Outcomes}, volume = {3}, year = {2010}, month = {2010 Mar}, pages = {159-64}, abstract = {

BACKGROUND: Recent studies have demonstrated an association between moderate kidney dysfunction and sudden cardiac death in people with cardiovascular disease.

METHODS AND RESULTS: The study was a longitudinal analysis among 4465 participants from the Cardiovascular Health Study without prevalent cardiovascular disease at baseline. Cystatin C and creatinine were measured from baseline sera. Sudden cardiac death (SCD) was defined as a sudden pulseless condition from a cardiac origin in a previously stable individual that occurred out of the hospital or in the emergency room. The association between cystatin C tertiles and SCD was determined with multivariate Cox proportional hazards. A similar analysis compared SCD incidence across creatinine-based estimated glomerular filtration rate (eGFR) tertiles. Over a median follow-up of 11.2 years, 91 adjudicated SCD events occurred. The annual incidence of SCD events increased across cystatin C tertiles: 10 events per 10 000 person years in tertile 1, 25 events per 10 000 person years in tertile 2, and 32 events per 10 000 person-years in the highest cystatin C tertile. These associations persisted after multivariate adjustment: hazards ratio=2.72; 95\% confidence interval, 1.44 to 5.16 in tertile 2 and hazards ratio=2.67; 95\% confidence interval, 1.33 to 5.35 in tertile 3. After multivariate adjustment, the rate of SCD also increased in a linear distribution across creatinine-based eGFR tertiles: 15 events per 10 000 person-years in tertile 1, 22 events per 10 000 person-years in tertile 2, and 27 events per 10 000 person-years in tertile 3. No significant associations, however, remained between creatinine-based eGFR and SCD after multivariable adjustment.

CONCLUSIONS: Impaired kidney function, as measured by cystatin C, has an independent association with SCD risk among elderly persons without clinical cardiovascular disease.

}, keywords = {Age Factors, Aged, Biomarkers, Chi-Square Distribution, Creatinine, Cystatin C, Death, Sudden, Cardiac, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney Diseases, Longitudinal Studies, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1941-7705}, doi = {10.1161/CIRCOUTCOMES.109.875369}, author = {Deo, Rajat and Sotoodehnia, Nona and Katz, Ronit and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and Kestenbaum, Bryan and Psaty, Bruce M and Siscovick, David S and Shlipak, Michael G} } @article {1091, title = {Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly.}, journal = {Nutr Metab Cardiovasc Dis}, volume = {20}, year = {2010}, month = {2010 Jan}, pages = {15-21}, abstract = {

BACKGROUND AND AIMS: Glycosylated hemoglobin (HbA(1c)) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA(1c) may be associated with an increased risk of death and cardiovascular mortality in older adults.

METHODS AND RESULTS: We evaluated the association between HbA(1c) with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals > or =65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA(1c) and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA(1c) groups were: 4.4\% per year, 4.3\% per year and 4.6\% per year for tertile 1 (< or =5.6\%), tertile 2 (5.61-6.20\%) and tertile 3 (> or =6.21\%), respectively. In unadjusted and fully adjusted analyses, baseline HbA(1c) was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95\% confidence interval 0.91-1.47] and hazard ratio: 1.31 [95\% confidence interval 0.90-1.93], respectively for the highest HbA(1c) tertile compared with the lowest).

CONCLUSION: These results suggest that HbA(1c) does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Disease Progression, Female, Glycated Hemoglobin A, Health Surveys, Heart Failure, Humans, Incidence, Male, Myocardial Infarction, Risk Factors, Statistics as Topic, Stroke, United States}, issn = {1590-3729}, doi = {10.1016/j.numecd.2009.02.007}, author = {Chonchol, M and Katz, R and Fried, L F and Sarnak, M J and Siscovick, D S and Newman, A B and Strotmeyer, E S and Bertoni, A and Shlipak, M G} } @article {1143, title = {Hip fractures and heart failure: findings from the Cardiovascular Health Study.}, journal = {Eur Heart J}, volume = {31}, year = {2010}, month = {2010 Jan}, pages = {77-84}, abstract = {

AIMS: The aim of the study was to find the epidemiology of hip fractures in heart failure. The increasing survival rate for patients with heart failure places them at risk for other diseases of ageing, including osteoporosis.

METHODS AND RESULTS: We included 5613 persons from the Cardiovascular Health Study (CHS) with an average of 11.5 year follow-up. We determined incidence rates and hazard ratios (HRs) in persons with heart failure compared with persons without heart failure and mortality hazards following these fractures. Annualized incidence rates for hip fractures were 14 per 1000 person-years in heart failure and 6.8 per 1000 person-years without heart failure. Unadjusted and multivariable adjusted HRs for hip fracture associated with heart failure in men were 1.87 (95\% CI 1.2-2.93) and 1.59 (95\% CI 0.93-2.72), respectively. Respective HRs for women were 1.75 (95\% CI 1.27-2.4) and 1.41 (95\% CI 0.98-2.03). Mortality hazard was approximately 2-fold greater in patients with heart failure and hip fracture compared with those having heart failure alone.

CONCLUSION: Persons with heart failure are at high risk for hip fractures. However, much of the association between hip fractures and heart failure is explained by shared risk factors. Hip fractures are a substantial contributor to mortality in men and women with heart failure.

}, keywords = {Aged, Female, Heart Failure, Hip Fractures, Humans, Incidence, Male, Risk Factors, United States}, issn = {1522-9645}, doi = {10.1093/eurheartj/ehp483}, author = {Carbone, Laura and B{\r u}zkov{\'a}, Petra and Fink, Howard A and Lee, Jennifer S and Chen, Zhao and Ahmed, Ali and Parashar, Susmita and Robbins, John R} } @article {1233, title = {Post hoc Parkinson{\textquoteright}s disease: identifying an uncommon disease in the Cardiovascular Health Study.}, journal = {Neuroepidemiology}, volume = {35}, year = {2010}, month = {2010}, pages = {241-9}, abstract = {

BACKGROUND: Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson{\textquoteright}s disease (PD), they typically have limited information for clinical diagnosis.

METHODS: We used combinations of self-report, International Classification of Diseases - 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.

RESULTS: We identified 60 cases with prevalent PD (1.0\%; 95\% confidence interval, CI = 0.8-1.3\%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95\% CI = 0.26-0.95) and for those who smoked >=50 pack-years (OR = 0.53; 95\% CI = 0.29-0.96). Estimates for smoking were similar when >=2 data sources were required. Estimates for self-report alone were attenuated towards null.

CONCLUSIONS: Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular System, Cohort Studies, Female, Health Status, Humans, Incidence, Male, Odds Ratio, Parkinson Disease, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1423-0208}, doi = {10.1159/000319895}, author = {Ton, T G and Jain, S and Boudreau, R and Thacker, E L and Strotmeyer, E S and Newman, A B and Longstreth, W T and Checkoway, H} } @article {1180, title = {Prevalence, incidence, and persistence of major depressive symptoms in the Cardiovascular Health Study.}, journal = {Aging Ment Health}, volume = {14}, year = {2010}, month = {2010 Mar}, pages = {168-76}, abstract = {

PURPOSE: To explore the association of major depressive symptoms with advancing age, sex, and self-rated health among older adults.

DESIGN AND METHODS: We analyzed 10 years of annual assessments in a longitudinal cohort of 5888 Medicare recipients in the Cardiovascular Health Study. Self-rated health was assessed with a single question, and subjects categorized as healthy or sick. Major depressive symptoms were assessed using the Center for Epidemiologic Studies Short Depression Scale, with subjects categorized as nondepressed (score < 10) or depressed (> or =10). Age-, sex-, and health-specific prevalence of depression and the probabilities of transition between depressed and nondepressed states were estimated.

RESULTS: The prevalence of a major depressive state was higher in women, and increased with advancing age. The probability of becoming depressed increased with advancing age among the healthy but not the sick. Women showed a greater probability than men of becoming depressed, regardless of health status. Major depressive symptoms persisted over one-year intervals in about 60\% of the healthy and 75\% of the sick, with little difference between men and women.

IMPLICATIONS: Clinically significant depressive symptoms occur commonly in older adults, especially women, increase with advancing age, are associated with poor self-rated health, and are largely intransigent. In order to limit the deleterious consequences of depression among older adults, increased attention to prevention, screening, and treatment is warranted. A self-rated health item could be used in clinical settings to refine the prognosis of late-life depression.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Cohort Studies, Depression, Depressive Disorder, Major, Female, Geriatric Assessment, Health Status, Humans, Incidence, Longitudinal Studies, Male, Personality Assessment, Prevalence, Psychiatric Status Rating Scales, Quality of Life, Sex Factors, Surveys and Questionnaires}, issn = {1364-6915}, doi = {10.1080/13607860903046537}, author = {Thielke, Stephen M and Diehr, Paula and Unutzer, Jurgen} } @article {1157, title = {Secondhand smoke, vascular disease, and dementia incidence: findings from the cardiovascular health cognition study.}, journal = {Am J Epidemiol}, volume = {171}, year = {2010}, month = {2010 Feb 01}, pages = {292-302}, abstract = {

Recent studies have found that smoking is associated with an increased risk of dementia, but the effects of secondhand smoke (SHS) on dementia risk are not known to have previously been studied. The authors used Cox proportional hazards marginal structural models to examine the association between self-reported lifetime household SHS exposure and risk of incident dementia over 6 years among 970 US participants in the Cardiovascular Health Cognition Study (performed from 1991 to 1999) who were never smokers and were free of clinical cardiovascular disease (CVD), dementia, and mild cognitive impairment at baseline. In addition, because prior studies have found that SHS is associated with increased risk of CVD and that CVD is associated with increased risk of dementia, the authors tested for interactions between SHS and measures of clinical and subclinical CVD on dementia risk. Moderate (16-25 years) and high (>25 years) SHS exposure levels were not independently associated with dementia risk; however, subjects with >25 years of SHS exposure and >25\% carotid artery stenosis had a 3-fold increase (hazard ratio = 3.00, 95\% confidence interval: 1.03, 9.72) in dementia risk compared with subjects with no/low (0-15 years) SHS exposure and < or =25\% carotid artery stenosis. High lifetime SHS exposure may increase the risk of dementia in elderly with undiagnosed CVD.

}, keywords = {Aged, Dementia, Female, Humans, Incidence, Male, Risk Factors, Tobacco Smoke Pollution, Vascular Diseases}, issn = {1476-6256}, doi = {10.1093/aje/kwp376}, author = {Barnes, Deborah E and Haight, Thaddeus J and Mehta, Kala M and Carlson, Michelle C and Kuller, Lewis H and Tager, Ira B} } @article {1184, title = {Serum albumin and risk of venous thromboembolism.}, journal = {Thromb Haemost}, volume = {104}, year = {2010}, month = {2010 Jul}, pages = {100-4}, abstract = {

The incidence of venous thromboembolism (VTE) is increased in patients with albuminuria. However, whether a low serum albumin concentration is associated with increased risk of VTE has been a matter of controversy. We determined the association of serum albumin with VTE incidence in two large, prospective, population-based cohorts: the Atherosclerosis Risk in Communities (ARIC) Study (n = 15,300) and the Cardiovascular Health Study (CHS) (n = 5,400). Validated VTE occurrence (n = 462 in ARIC and n = 174 in CHS) was ascertained during follow-up. In both studies, after adjustment for age, sex, race, use of hormone replacement therapy, estimated glomerular filtration rate, history of cancer, and diabetes, serum albumin tended to be associated inversely with VTE. The adjusted hazard ratio per standard deviation lower albumin was 1.18 (95\% confidence interval [CI] = 1.08, 1.31) in ARIC and 1.10 (95\% CI = 0.94, 1.29) in CHS. The hazard ratio for albumin below (vs. above) the fifth percentile was 1.28 (95\% CI = 0.90, 1.84) in ARIC and 1.80 (95\% CI = 1.11, 2.93) in CHS. In conclusion, low serum albumin was a modest marker of increased VTE risk. The observed association likely does not reflect cause and effect, but rather that low serum albumin reflects a hyperinflammatory or hypercoagulable state. Whether this association has clinical relevance warrants further study.

}, keywords = {Aged, Biomarkers, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Risk Factors, Serum Albumin, United States, Venous Thromboembolism}, issn = {2567-689X}, doi = {10.1160/TH09-12-0856}, author = {Folsom, Aaron R and Lutsey, Pamela L and Heckbert, Susan R and Cushman, Mary} } @article {1246, title = {Subclinical thyroid dysfunction and incident hip fracture in older adults.}, journal = {Arch Intern Med}, volume = {170}, year = {2010}, month = {2010 Nov 22}, pages = {1876-83}, abstract = {

BACKGROUND: Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture.

METHODS: Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95\% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline.

RESULTS: During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95\% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99-11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95\% CI, 1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27-4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women.

CONCLUSIONS: Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown.

}, keywords = {Aged, Female, Follow-Up Studies, Hip Fractures, Humans, Hyperthyroidism, Hypothyroidism, Incidence, Male, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Distribution, Thyrotropin, United States}, issn = {1538-3679}, doi = {10.1001/archinternmed.2010.424}, author = {Lee, Jennifer S and B{\r u}zkov{\'a}, Petra and Fink, Howard A and Vu, Joseph and Carbone, Laura and Chen, Zhao and Cauley, Jane and Bauer, Doug C and Cappola, Anne R and Robbins, John} } @article {1257, title = {Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.}, journal = {Ann Intern Med}, volume = {153}, year = {2010}, month = {2010 Dec 21}, pages = {790-9}, abstract = {

BACKGROUND: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative.

OBJECTIVE: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes.

DESIGN: Prospective cohort study from 1992 to 2006.

SETTING: Four U.S. communities.

PATIENTS: 3736 adults in the Cardiovascular Health Study.

MEASUREMENTS: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women.

RESULTS: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9\% across quintiles; P = 0.040), lower triglyceride levels (-19.0\%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7\%; P < 0.001), lower C-reactive protein levels (-13.8\%; P = 0.05), and lower insulin resistance (-16.7\%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95\% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort.

LIMITATION: Results could be affected by measurement error or residual confounding.

CONCLUSION: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

}, keywords = {Adiposity, Aged, C-Reactive Protein, Cholesterol, Cholesterol, HDL, Dairy Products, Diabetes Mellitus, Type 2, Fatty Acids, Monounsaturated, Feeding Behavior, Female, Humans, Incidence, Insulin Resistance, Male, Prospective Studies, Risk Factors, Triglycerides, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-153-12-201012210-00005}, author = {Mozaffarian, Dariush and Cao, Haiming and King, Irena B and Lemaitre, Rozenn N and Song, Xiaoling and Siscovick, David S and Hotamisligil, G{\"o}khan S} } @article {1247, title = {Validation of an atrial fibrillation risk algorithm in whites and African Americans.}, journal = {Arch Intern Med}, volume = {170}, year = {2010}, month = {2010 Nov 22}, pages = {1909-17}, abstract = {

BACKGROUND: We sought to validate a recently published risk algorithm for incident atrial fibrillation (AF) in independent cohorts and other racial groups.

METHODS: We evaluated the performance of a Framingham Heart Study (FHS)-derived risk algorithm modified for 5-year incidence of AF in the FHS (n = 4764 participants) and 2 geographically and racially diverse cohorts in the age range 45 to 95 years: AGES (the Age, Gene/Environment Susceptibility-Reykjavik Study) (n = 4238) and CHS (the Cardiovascular Health Study) (n = 5410, of whom 874 [16.2\%] were African Americans). The risk algorithm included age, sex, body mass index, systolic blood pressure, electrocardiographic PR interval, hypertension treatment, and heart failure.

RESULTS: We found 1359 incident AF events in 100 074 person-years of follow-up. Unadjusted 5-year event rates differed by cohort (AGES, 12.8 cases/1000 person-years; CHS whites, 22.7 cases/1000 person-years; and FHS, 4.5 cases/1000 person-years) and by race (CHS African Americans, 18.4 cases/1000 person-years). The strongest risk factors in all samples were age and heart failure. The relative risks for incident AF associated with risk factors were comparable across cohorts and race groups. After recalibration for baseline incidence and risk factor distribution, the Framingham algorithm, reported in C statistic, performed reasonably well in all samples: AGES, 0.67 (95\% confidence interval [CI], 0.64-0.71); CHS whites, 0.68 (95\% CI, 0.66-0.70); and CHS African Americans, 0.66 (95\% CI, 0.61-0.71). Risk factors combined in the algorithm explained between 47.0\% (AGES) and 63.6\% (FHS) of the population-attributable risk.

CONCLUSIONS: Risk of incident AF in community-dwelling whites and African Americans can be assessed reliably by routinely available and potentially modifiable clinical variables. Seven risk factors accounted for up to 64\% of risk.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Algorithms, Atrial Fibrillation, Blood Pressure, Body Mass Index, Cohort Studies, Electrocardiography, Europe, European Continental Ancestry Group, Female, Follow-Up Studies, Heart Failure, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Proportional Hazards Models, Risk Factors, Sex Factors, Systole, United States}, issn = {1538-3679}, doi = {10.1001/archinternmed.2010.434}, author = {Schnabel, Renate B and Aspelund, Thor and Li, Guo and Sullivan, Lisa M and Suchy-Dicey, Astrid and Harris, Tamara B and Pencina, Michael J and D{\textquoteright}Agostino, Ralph B and Levy, Daniel and Kannel, William B and Wang, Thomas J and Kronmal, Richard A and Wolf, Philip A and Burke, Gregory L and Launer, Lenore J and Vasan, Ramachandran S and Psaty, Bruce M and Benjamin, Emelia J and Gudnason, Vilmundur and Heckbert, Susan R} } @article {1194, title = {Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {3}, year = {2010}, month = {2010 Jul}, pages = {495-502}, abstract = {

BACKGROUND: The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model.

METHODS AND RESULTS: Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5\%) participants developed heart failure over 5 years versus 364 (6.8\%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2\% versus 2.8\%, 9.0\% versus 7.0\%, 15.9\% versus 13.7\%, and 24.6\% versus 30.8\% for the <5\%, 5\% to 10\%, 10\% to 20\%, and >20\% 5-year risk categories, respectively. The Hosmer-Lemeshow chi(2) was 14.72 (degrees of freedom, 10; P=0.14), and the C index was 0.74 (95\% CI, 0.72 to 0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however, risk was underestimated in white men, especially in the 5\% to 10\% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results.

CONCLUSIONS: The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to whom to target heart failure prevention efforts.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Cause of Death, Cohort Studies, Confidence Intervals, Disease Progression, Echocardiography, Doppler, Female, Heart Failure, Humans, Incidence, Male, Models, Statistical, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Survival Analysis, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.109.904300}, author = {Kalogeropoulos, Andreas and Psaty, Bruce M and Vasan, Ramachandran S and Georgiopoulou, Vasiliki and Smith, Andrew L and Smith, Nicholas L and Kritchevsky, Stephen B and Wilson, Peter W F and Newman, Anne B and Harris, Tamara B and Butler, Javed} } @article {1278, title = {Association of incident cardiovascular disease with progression of sleep-disordered breathing.}, journal = {Circulation}, volume = {123}, year = {2011}, month = {2011 Mar 29}, pages = {1280-6}, abstract = {

BACKGROUND: Prospective data suggest that sleep-disordered breathing enhances risk for incident and recurrent cardiovascular disease (CVD). However, a reverse causal pathway whereby incident CVD causes or worsens sleep-disordered breathing has not been studied.

METHODS AND RESULTS: A total of 2721 Sleep Heart Health Study participants (mean age 62, standard deviation=10 years; 57\% women; 23\% minority) without CVD at baseline underwent 2 polysomnograms 5 years apart. Incident CVD events, including myocardial infarction, congestive heart failure, and stroke, were ascertained and adjudicated. The relation of incident CVD to change in apnea-hypopnea index between the 2 polysomnograms was tested with general linear models, with adjustment for age, sex, race, study center, history of diabetes mellitus, change in body mass index, change in neck circumference, percent sleep time spent in supine sleep, and time between the 2 polysomnograms. Incident CVD occurred in 95 participants between the first and second polysomnograms. Compared with participants without incident CVD, those with incident CVD experienced larger increases in apnea-hypopnea index between polysomnograms. The difference in adjusted mean apnea-hypopnea index change between subjects with and without incident CVD was 2.75 events per hour (95\% confidence interval, 0.26 to 5.24; P=0.032). This association persisted after subjects with central sleep apnea were excluded. Compared with participants without incident CVD, participants with incident CVD had greater increases in both mean obstructive and central apnea indices, by 1.75 events per hour (95\% confidence interval, 0.10 to 1.75; P=0.04) and by 1.07 events per hour (95\% confidence interval, 0.40 to 1.74; P=0.001), respectively.

CONCLUSIONS: In a diverse, community-based sample of middle-aged and older adults, incident CVD was associated with worsening sleep-disordered breathing over 5 years.

}, keywords = {Aged, Cardiovascular Diseases, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Polysomnography, Risk Factors, Sleep Apnea Syndromes}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.110.974022}, author = {Chami, Hassan A and Resnick, Helaine E and Quan, Stuart F and Gottlieb, Daniel J} } @article {1331, title = {Carotid intima-media thickness, electrocardiographic left ventricular hypertrophy, and incidence of intracerebral hemorrhage.}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Nov}, pages = {3075-9}, abstract = {

BACKGROUND AND PURPOSE: Carotid intima-media thickness and electrocardiographic left ventricular hypertrophy are 2 subclinical cardiovascular disease measures associated with increased risk of total and ischemic strokes. Increased intima-media thickness and electrocardiographic left ventricular hypertrophy also may reflect end-organ hypertensive effects. Information is scant on the associations of these subclinical measures with intracerebral hemorrhage (ICH). We hypothesized that greater carotid intima-media thickness and the presence of electrocardiographic left ventricular hypertrophy would be independently associated with increased ICH incidence.

METHODS: Among 18,155 participants initially free of stroke in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS), we assessed carotid intima-media thickness, carotid plaque, and electrocardiographic left ventricular hypertrophy. Over a median of 18 years of follow-up, 162 incident ICH events occurred.

RESULTS: After adjustment for other ICH risk factors, carotid intima-media thickness was associated positively with incidence of ICH in both ARIC and CHS. The risk was lowest in study-specific Quartile 1, elevated 1.6- to 2.6-fold in Quartiles 2 to 3, and elevated 2.5 to 3.7-fold in Quartile 4 (P<0.05 for both studies). In CHS, having a carotid plaque was associated with a 2-fold (95\% CI, 1.1-3.4) greater ICH risk than having no plaque, but only 1.2-fold (95\% CI, 0.76-2.0) greater ICH risk in ARIC. Electrocardiographic left ventricular hypertrophy carried a hazard ratio of ICH of 1.7 (95\% CI, 0.77-3.7) in CHS and 2.8 (95\% CI, 1.2-6.4) in ARIC.

CONCLUSIONS: Our data suggest that people with carotid atherosclerosis and possibly left ventricular hypertrophy are at increased risk not only of ischemic stroke, but also of ICH.

}, keywords = {Carotid Intima-Media Thickness, Cerebral Hemorrhage, Cohort Studies, Electrocardiography, Female, Follow-Up Studies, Humans, Hypertrophy, Left Ventricular, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.623157}, author = {Folsom, Aaron R and Yatsuya, Hiroshi and Psaty, Bruce M and Shahar, Eyal and Longstreth, W T} } @article {1309, title = {Circulating long-chain ω-3 fatty acids and incidence of congestive heart failure in older adults: the cardiovascular health study: a cohort study.}, journal = {Ann Intern Med}, volume = {155}, year = {2011}, month = {2011 Aug 02}, pages = {160-70}, abstract = {

BACKGROUND: Few previous studies have evaluated associations between long-chain ω-3 fatty acids and incidence of congestive heart failure (CHF), and those that have are typically based on diet questionnaires and yield conflicting results. Circulating fatty acid concentrations provide objective biomarkers of exposure.

OBJECTIVE: To determine whether plasma phospholipid concentrations of long-chain ω-3 fatty acids, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), were associated with incident CHF.

DESIGN: Prospective cohort study.

SETTING: 4 U.S. communities.

PATIENTS: 2735 U.S. adults without prevalent heart disease who were enrolled in the Cardiovascular Health Study from 1992 to 2006.

MEASUREMENTS: Plasma phospholipid fatty acid concentrations and other cardiovascular risk factors were measured in 1992 by using standardized methods. Relationships with incident CHF (555 cases during 26 490 person-years, adjudicated by using medical records) were assessed by using Cox proportional hazards models.

RESULTS: After multivariate adjustment, plasma phospholipid EPA concentration was inversely associated with incident CHF; risk was approximately 50\% lower in the highest versus the lowest quartile (hazard ratio [HR], 0.52 [95\% CI, 0.38 to 0.72]; P for trend = 0.001). In similar analyses, trends toward lower risk were seen for DPA (HR, 0.76 [CI, 0.56 to 1.04]; P for trend = 0.057) and total long-chain ω-3 fatty acids (HR, 0.70 [CI, 0.49 to 0.99]; P for trend = 0.062) but not for DHA (HR, 0.84 [CI, 0.58 to 1.21]; P for trend = 0.38). In analyses censored to the middle of follow-up (7 years) to minimize exposure misclassification over time, multivariate-adjusted HRs were 0.48 for EPA (CI, 0.32 to 0.71; P for trend = 0.005), 0.61 for DPA (CI, 0.39 to 0.95; P for trend = 0.033), 0.64 for DHA (CI, 0.40 to 1.04; P for trend = 0.057), and 0.51 for total ω-3 fatty acids (CI, 0.32 to 0.80; P for trend = 0.003).

LIMITATIONS: Temporal changes in fatty acid concentrations over time may have caused underestimation of associations. Unmeasured or imperfectly measured covariates may have caused residual confounding.

CONCLUSION: Circulating individual and total ω-3 fatty acid concentrations are associated with lower incidence of CHF in older adults.

PRIMARY FUNDING SOURCE: National Institutes of Health.

}, keywords = {Aged, Biomarkers, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Feeding Behavior, Heart Failure, Humans, Incidence, Proportional Hazards Models, Prospective Studies, Risk Factors}, issn = {1539-3704}, doi = {10.7326/0003-4819-155-3-201108020-00006}, author = {Mozaffarian, Dariush and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Spiegelman, Donna and Sacks, Frank M and Rimm, Eric B and Siscovick, David S} } @article {1241, title = {Diastolic blood pressure levels and ischemic stroke incidence in older adults with white matter lesions.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Jan}, pages = {74-81}, abstract = {

BACKGROUND: The optimal blood pressure level to minimize the risk of ischemic stroke (IS) in older adults is undetermined. Cerebral white matter lesions (WML), prevalent in older adults, may be a marker for vulnerability to IS. We aimed at determining the relationship between diastolic blood pressure (DBP) levels and IS in the presence of WML.

METHODS: The Cardiovascular Health Study population (N = 3,345, age >= 65 years, N = 3,345) was followed between 1989 and 2002 for IS incidence. Survival analysis included quintiles of DBP analyzed within WML levels controlling for age and cardiovascular disease.

RESULTS: DBP had no effect on IS incidence in low WML levels but had a marginally significant J-curve relationship with IS in high WML levels: the adjusted hazard ratio for IS in the lowest (<63 mmHg) and highest (>= 80) DBP quintiles compared with the third (nadir, 69-73 mmHg) was 1.64 (95\% confidence interval: 0.93-2.9) and 1.83 (95\% confidence interval: 1.06-3.15), respectively.

CONCLUSIONS: In older adults with low-grade WML, low DBP may not pose a risk for IS. However, in high-grade WML, IS risk may increase in DBP less than 69 mmHg but is highest more than 80 mmHg. People with high-grade WML may be at risk of IS in high and low DBP.

}, keywords = {Aged, Aged, 80 and over, Brain, Brain Ischemia, Cerebrovascular Circulation, Diastole, Female, Humans, Incidence, Male, Multivariate Analysis, Stroke}, issn = {1758-535X}, doi = {10.1093/gerona/glq166}, author = {Reshef, Shoshana and Fried, Linda and Beauchamp, Norman and Scharfstein, Daniel and Reshef, Daniel and Goodman, Steven} } @article {1339, title = {Fasting and post-glucose load measures of insulin resistance and risk of ischemic stroke in older adults.}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Dec}, pages = {3347-51}, abstract = {

BACKGROUND AND PURPOSE: Few studies have assessed post-glucose load measures of insulin resistance and ischemic stroke risk, and data are sparse for older adults. We investigated whether fasting and post-glucose load measures of insulin resistance were related to incident ischemic stroke in nondiabetic, older adults.

METHODS: Participants were men and women in the Cardiovascular Health Study, age 65+ years and without prevalent diabetes or stroke at baseline, followed for 17 years for incident ischemic stroke. The Gutt insulin sensitivity index was calculated from baseline body weight and from fasting and 2-hour postload insulin and glucose; a lower Gutt index indicates higher insulin resistance.

RESULTS: Analyses included 3442 participants (42\% men) with a mean age of 73 years. Incidence of ischemic stroke was 9.8 strokes per 1000 person-years. The relative risk (RR) for lowest quartile versus highest quartile of Gutt index was 1.64 (95\% CI, 1.24-2.16), adjusted for demographics and prevalent cardiovascular and kidney disease. Similarly, the adjusted RR for highest quartile versus lowest quartile of 2-hour glucose was 1.84 (95\% CI, 1.39-2.42). In contrast, the adjusted RR for highest quartile versus lowest quartile of fasting insulin was 1.10 (95\% CI, 0.84-1.46).

CONCLUSIONS: In nondiabetic, older adults, insulin resistance measured by Gutt index or 2-hour glucose, but not by fasting insulin, was associated with risk of incident ischemic stroke.

}, keywords = {Aged, Aged, 80 and over, Blood Glucose, Body Mass Index, Brain Ischemia, Fasting, Female, Humans, Incidence, Insulin Resistance, Male, Risk, Stroke}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.620773}, author = {Thacker, Evan L and Psaty, Bruce M and McKnight, Barbara and Heckbert, Susan R and Longstreth, W T and Mukamal, Kenneth J and Meigs, James B and de Boer, Ian H and Boyko, Edward J and Carnethon, Mercedes R and Kizer, Jorge R and Tracy, Russell P and Smith, Nicholas L and Siscovick, David S} } @article {1262, title = {Gender differences between the Minnesota code and Novacode electrocardiographic prognostication of coronary heart disease in the cardiovascular health study.}, journal = {Am J Cardiol}, volume = {107}, year = {2011}, month = {2011 Mar 15}, pages = {817-820.e1}, abstract = {

The Minnesota Code (MC) and Novacode (Nova) are the most widely used electrocardiographic (ECG) classification systems. The comparative strengths of their classifications for Q- and ST-T-wave abnormalities in predicting coronary heart disease (CHD) events and total mortality have not been evaluated separately by gender. We studied standard 12-lead electrocardiograms at rest from 4,988 participants in the Cardiovascular Health Study. Average age at baseline was 73 years, 60\% of participants were women 85\% were white, and 22\% had a history of cardiovascular disease or presence of ECG myocardial infarction by MC or Nova. Starting in 1989 with an average 17-year follow-up, 65\% of participants died and 33\% had incident CHD in a cohort free of cardiovascular disease at baseline. Of these, electrocardiograms with major Q-wave or major ST-T abnormalities by MC or Nova predicted increased risk for CHD events and total mortality with no significant differences in predictability between men and women. The study also found that women had fewer major Q-wave changes but more major ST-T abnormalities than men. However, there were no gender differences in predicting CHD events and total mortality. In conclusion, ECG classification systems for myocardial infarction/ischemia abnormalities by MC or Nova are valuable and useful for men and women in clinical trials and epidemiologic studies.

}, keywords = {Aged, Coronary Disease, Electrocardiography, Female, Humans, Incidence, Male, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2010.11.004}, author = {Zhang, Zhu-Ming and Prineas, Ronald J and Case, Doug and Psaty, Bruce M and Suzuki, Takeki and Burke, Gregory L} } @article {1254, title = {Measures of adiposity and future risk of ischemic stroke and coronary heart disease in older men and women.}, journal = {Am J Epidemiol}, volume = {173}, year = {2011}, month = {2011 Jan 01}, pages = {10-25}, abstract = {

The relation between measures of general and central adiposity and individual cardiovascular endpoints remains understudied in older adults. This study investigated the association of measures of body size and composition with incident ischemic stroke or coronary heart disease (1989-2007) in 3,754 community-dwelling US adults aged 65-100 years. Standardized anthropometry and bioelectric impedance measurements were obtained at baseline. Body mass index at age 50 years (BMI50) was calculated on the basis of recalled weight. Although only waist/hip ratio was significantly associated with ischemic stroke in quintile analysis in women, dichotomized body mass index (BMI) (>= 30 kg/m{\texttwosuperior}) was the only significant predictor in men. For coronary heart disease, there were significant positive adjusted associations for all adiposity measures, without interaction by sex. This was true for both quintiles and conventional cutpoints for obesity, although BMI-defined overweight (25-29.9 kg/m{\texttwosuperior} was significant at midlife but not at baseline. Strengths of association for extreme quintiles (quintile 5 vs. quintile 1) were broadly comparable, but the highest effect estimates were for waist/hip ratio (hazard ratio = 1.56, 95\% confidence interval: 1.25, 1.94) and BMI50 (hazard ratio = 1.71, 95\% confidence interval: 1.37, 2.14), both of which remained significant after adjustment for mediators, BMI, or each other. Whether these differences translate to better risk prediction will require meta-analytical approaches, as will determination of prognostic cutpoints.

}, keywords = {Adiposity, Age Factors, Aged, Aged, 80 and over, Brain Ischemia, Coronary Disease, Female, Humans, Incidence, Male, Middle Aged, Obesity, Prevalence, Retrospective Studies, Risk Factors, Sex Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwq311}, author = {Kizer, Jorge R and Biggs, Mary L and Ix, Joachim H and Mukamal, Kenneth J and Zieman, Susan J and de Boer, Ian H and Mozaffarian, Dariush and Barzilay, Joshua I and Strotmeyer, Elsa S and Luchsinger, Jos{\'e} A and Elkind, Mitchell S V and Longstreth, W T and Kuller, Lewis H and Siscovick, David S} } @article {1332, title = {Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).}, journal = {Stroke}, volume = {42}, year = {2011}, month = {2011 Dec}, pages = {3363-8}, abstract = {

BACKGROUND AND PURPOSE: Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations.

METHODS: We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages>=65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors.

RESULTS: Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95\% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke.

CONCLUSIONS: Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.

}, keywords = {Aged, Aged, 80 and over, Brain Ischemia, Female, Health Status Disparities, Humans, Incidence, Longitudinal Studies, Male, Poverty, Residence Characteristics, Risk, Risk Factors, Social Class, Social Environment, Socioeconomic Factors, Stroke, Urban Population}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.111.622134}, author = {Brown, Arleen F and Liang, Li-Jung and Vassar, Stefanie D and Stein-Merkin, Sharon and Longstreth, W T and Ovbiagele, Bruce and Yan, Tingjian and Escarce, Jos{\'e} J} } @article {1242, title = {N-terminal pro-B-type natriuretic peptide is associated with sudden cardiac death risk: the Cardiovascular Health Study.}, journal = {Heart Rhythm}, volume = {8}, year = {2011}, month = {2011 Feb}, pages = {228-33}, abstract = {

BACKGROUND: Sudden cardiac death (SCD), the cause of 250,000-450,000 deaths per year, is a major public health problem. The majority of those affected do not have a prior cardiovascular diagnosis. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure and mortality as well as with sudden death in women.

OBJECTIVE: The purpose of this study was to examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population.

METHODS: The risk of SCD associated with baseline NT-proBNP was examined in 5,447 participants. Covariate-adjusted Cox model regressions were used to estimate the hazard ratios of developing SCD as a function of baseline NT-proBNP.

RESULTS: Over a median follow-up of 12.5 years (maximum 16), there were 289 cases of SCD. Higher NT-proBNP levels were strongly associated with SCD, with an unadjusted hazard ratio of 4.2 (95\% confidence interval [2.9, 6.1]; P <.001) in the highest quintile compared with in the lowest. NT-proBNP remained associated with SCD even after adjustment for numerous clinical characteristics and risk factors (age, sex, race, and other associated conditions), with an adjusted hazard ratio for the fifth versus the first quintile of 2.5 (95\% confidence interval [1.6, 3.8]; P <.001).

CONCLUSION: NT-proBNP provides information regarding the risk of SCD in a community-based population of older adults, beyond other traditional risk factors. This biomarker may ultimately prove useful in targeting the population at risk with aggressive medical management of comorbid conditions.

}, keywords = {Age Distribution, Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Confidence Intervals, Death, Sudden, Cardiac, Female, Humans, Incidence, Kaplan-Meier Estimate, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Sex Distribution, Time Factors, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2010.10.038}, author = {Patton, Kristen K and Sotoodehnia, Nona and DeFilippi, Christopher and Siscovick, David S and Gottdiener, John S and Kronmal, Richard A} } @article {1268, title = {Predictive value of depressive symptoms and B-type natriuretic peptide for new-onset heart failure and mortality.}, journal = {Am J Cardiol}, volume = {107}, year = {2011}, month = {2011 Mar 01}, pages = {723-9}, abstract = {

Depression and natriuretic peptides predict heart failure (HF) progression, but the unique contributions of depression and biomarkers associated with HF outcomes are not known. The present study determined the additive predictive value of depression and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) for new-onset HF in HF-free subjects and mortality in patients with HF. The participants in the Cardiovascular Health Study were assessed for depressive symptoms using the Center for Epidemiologic Studies Depression Scale and NT-proBNP using an electrochemiluminescence immunoassay. The validated cutoff values for depression (Center for Epidemiologic Studies Depression Scale >=8) and NT-proBNP (>=190 pg/ml) were used. The risks of incident HF and mortality (cardiovascular disease-related and all-cause) were examined during a median follow-up of 11 years, adjusting for demographics, clinical factors, and health behaviors. In patients with HF (n = 208), depression was associated with an elevated risk of cardiovascular disease mortality (hazard ratios [HR] 2.07, 95\% confidence interval [CI] 1.31 to 3.27) and all-cause mortality (HR 1.49, 95\% CI 1.05 to 2.11), independent of the NT-proBNP level and covariates. The combined presence of depression and elevated NT-proBNP was associated with substantially elevated covariate-adjusted risks of cardiovascular disease mortality (HR 5.42, 95\% CI 2.38 to 12.36) and all-cause mortality (HR 3.72, 95\% CI 2.20 to 6.37). In the 4,114 HF-free subjects, new-onset HF was independently predicted by an elevated NT-proBNP level (HR 2.27, 95\% CI 1.97 to 2.62) but not depression (HR 1.08, 95\% CI 0.92 to 1.26) in covariate-adjusted analysis. In conclusion, depression and NT-proBNP displayed additive predictive value for mortality in patients with HF. These associations can be explained by complementary pathophysiologic mechanisms. The presence of both elevated depression and NT-proBNP levels might improve the identification of patients with HF with a high risk of mortality.

}, keywords = {Aged, Depression, Disease Progression, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Natriuretic Peptide, Brain, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2010.10.055}, author = {van den Broek, Krista C and deFilippi, Christopher R and Christenson, Robert H and Seliger, Stephen L and Gottdiener, John S and Kop, Willem J} } @article {1293, title = {Predictors of thyroid hormone initiation in older adults: results from the cardiovascular health study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {66}, year = {2011}, month = {2011 Jul}, pages = {809-14}, abstract = {

BACKGROUND: Despite widespread use, there are no data on initiation of thyroid hormone use in older people. We report the prevalence of thyroid hormone use and predictors of thyroid hormone initiation in a population of older men and women.

METHODS: Thyroid hormone medication data were collected annually from 1989 to 2006 in community-dwelling individuals aged 65 years and older enrolled in the Cardiovascular Health Study (N = 5,888). Associations of age, sex, race, body mass index, education, and coronary heart disease with initiation were evaluated using discrete-time survival analysis.

RESULTS: In 1989-1990, 8.9\% (95\% confidence interval 8.1\%-9.7\%) of participants were taking a thyroid hormone preparation, increasing to 20.0\% (95\% confidence interval 8.2\%-21.8\%) over 16 years. The average initiation rate was 1\% per year. The initiation rate was nonlinear with age, and those aged 85 years and older initiated thyroid hormone more than twice as frequently as those aged 65-69 years (hazard ratio = 2.34; 95\% confidence interval 1.43-3.85). White women were more likely to initiate thyroid hormone than any other race and sex group. Higher body mass index was independently associated with higher risk for initiation (p = .002) as was greater education (p = .02) and prevalent coronary heart disease (p = .03).

CONCLUSIONS: Thyroid hormone use is common in older people. The indications and benefits of thyroid hormone use in older individuals with the highest rate of thyroid hormone initiation-the oldest old, overweight and obese individuals, and those with coronary heart disease-should be investigated.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Hypothyroidism, Incidence, Male, Prevalence, Prognosis, Retrospective Studies, Risk Factors, Sex Factors, Thyroid Hormones, Thyroxine, Time Factors, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glr063}, author = {Somwaru, Lily L and Arnold, Alice M and Cappola, Anne R} } @article {1321, title = {The relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {4}, year = {2011}, month = {2011 Nov}, pages = {733-9}, abstract = {

BACKGROUND: The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals.

METHODS AND RESULTS: In 880 participants in the Cardiovascular Health Study (mean age, 77{\textpm}6 years; 48\% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55\%); HF with preserved EF (HFPEF; n=175, EF >=55\%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12{\textpm}4 years (range, 3-17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups.

CONCLUSIONS: In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

}, keywords = {Aged, Aged, 80 and over, Aging, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Collagen, Collagen Type I, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Peptide Fragments, Peptides, Predictive Value of Tests, Procollagen, Prospective Studies, Stroke Volume, Survival Rate}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.111.962027}, author = {Barasch, Eddy and Gottdiener, John S and Aurigemma, Gerard and Kitzman, Dalane W and Han, Jing and Kop, Willem J and Tracy, Russell P} } @article {1255, title = {Relationship of abnormal heart rate turbulence and elevated CRP to cardiac mortality in low, intermediate, and high-risk older adults.}, journal = {J Cardiovasc Electrophysiol}, volume = {22}, year = {2011}, month = {2011 Feb}, pages = {122-7}, abstract = {

INTRODUCTION: We examined whether heart rate turbulence (HRT) and C-reactive protein (CRP) add to traditional risk factors for cardiac mortality in older adults at low, intermediate, and high risk.

METHODS AND RESULTS: One thousand two hundred and seventy-two individuals, age >= 65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated CRP (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical cardiovascular disease. Having TS + TO abnormal compared to both normal was associated with cardiac mortality in the low-risk group [HR 7.9, 95\% confidence interval (CI) 2.8-22.5, (P < 0.001)]. In the high and intermediate risk groups, abnormal TS and TS + TO ([HR 2.2, 95\% CI 1.5-4.0, P = 0.016] and [HR 2.7, 95\% CI 1.2-5.9, P = 0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low-risk individuals [HR 2.5, 95\% CI 1.3-5.1, P = 0.009]. Among low risk, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT.

CONCLUSIONS: Abnormal HRT independently adds to risk stratification of low, intermediate and high-risk individuals, but HRT and CRP appear to both add to stratification of those considered low risk.

}, keywords = {Aged, C-Reactive Protein, Cardiovascular Diseases, Comorbidity, Electrocardiography, Ambulatory, Female, Humans, Incidence, Male, Risk Assessment, Risk Factors, Statistics as Topic, Survival Analysis, Survival Rate, United States, Ventricular Premature Complexes}, issn = {1540-8167}, doi = {10.1111/j.1540-8167.2010.01967.x}, author = {Stein, Phyllis K and Barzilay, Joshua I} } @article {1350, title = {Vitamin D, parathyroid hormone, and sudden cardiac death: results from the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {58}, year = {2011}, month = {2011 Dec}, pages = {1021-8}, abstract = {

Recent studies have demonstrated greater risks of cardiovascular events and mortality among persons who have lower 25-hydroxyvitamin D (25-OHD) and higher parathyroid hormone (PTH) levels. We sought to evaluate the association between markers of mineral metabolism and sudden cardiac death (SCD) among the 2312 participants from the Cardiovascular Health Study who were free of clinical cardiovascular disease at baseline. We estimated associations of baseline 25-OHD and PTH concentrations individually and in combination with SCD using Cox proportional hazards models after adjustment for demographics, cardiovascular risk factors, and kidney function. During a median follow-up of 14 years, there were 73 adjudicated SCD events. The annual incidence of SCD was greater among subjects who had lower 25-OHD concentrations, 2 events per 1000 for 25-OHD >=20 ng/mL and 4 events per 1000 for 25-OHD <20 ng/mL. Similarly, SCD incidence was greater among subjects who had higher PTH concentrations, 2 events per 1000 for PTH <65 pg/mL and 4 events per 1000 for PTH >=65 pg/mL. Multivariate adjustment attenuated associations of 25-OHD and PTH with SCD. Finally, 267 participants (11.7\% of the cohort) had high PTH and low 25-OHD concentrations. This combination was associated with a >2-fold risk of SCD after adjustment (hazard ratio: 2.19 [95\% CI: 1.17-4.10]; P=0.017) compared with participants with normal levels of PTH and 25-OHD. The combination of lower 25-OHD and higher PTH concentrations appears to be associated independently with SCD risk among older adults without cardiovascular disease.

}, keywords = {Aged, Cardiovascular Diseases, Comorbidity, Death, Sudden, Cardiac, Diabetes Mellitus, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Kidney, Male, Middle Aged, Minerals, Parathyroid Hormone, Proportional Hazards Models, Risk Factors, Socioeconomic Factors, United States, Vitamin D}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.111.179135}, author = {Deo, Rajat and Katz, Ronit and Shlipak, Michael G and Sotoodehnia, Nona and Psaty, Bruce M and Sarnak, Mark J and Fried, Linda F and Chonchol, Michel and de Boer, Ian H and Enquobahrie, Daniel and Siscovick, David and Kestenbaum, Bryan} } @article {1344, title = {Adiposity and incident heart failure in older adults: the cardiovascular health study.}, journal = {Obesity (Silver Spring)}, volume = {20}, year = {2012}, month = {2012 Sep}, pages = {1936-41}, abstract = {

While several studies have reported a positive association between overall adiposity and heart failure (HF) risk, limited and inconsistent data are available on the relation between central adiposity and incident HF in older adults. We sought to examine the association between waist circumference (WC) and incident HF and assess whether sex modifies the relation between WC and HF. Prospective study using data on 4,861 participants of the Cardiovascular Health Study (1989-2007). HF was adjudicated by a committee using information from medical records and medications. We used Cox proportional hazard models to compute hazard ratio (HR). The mean age was 73.0 years for men and 72.3 years for women; 42.5\% were men and 15.3\% were African Americans. WC was positively associated with an increased risk of HF: each standard deviation of WC was associated with a 14\% increased risk of HF (95\% CI: 3\%-26\%) in a multivariable model. There was not a statistically significant sex-by-WC interaction (P = 0.081). BMI was positively associated with incident HF (HR: 1.22 (95\% CI: 1.15-1.29) per standard deviation increase of BMI); however, this association was attenuated and became nonstatistically significant upon additional adjustment for WC (HR: 1.09 (95\% CI: 0.99-1.21)). In conclusion, a higher WC is associated with an increased risk of HF independent of BMI in community-living older men and women.

}, keywords = {Adiposity, Aged, Aging, Body Fat Distribution, Body Mass Index, Female, Heart Failure, Humans, Incidence, Independent Living, Male, Obesity, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Factors, Sex Factors, United States, Waist Circumference}, issn = {1930-739X}, doi = {10.1038/oby.2011.320}, author = {Djouss{\'e}, Luc and Bartz, Traci M and Ix, Joachim H and Zieman, Susan J and Delaney, Joseph A and Mukamal, Kenneth J and Gottdiener, John S and Siscovick, David S and Kizer, Jorge R} } @article {1380, title = {Association of fetuin-a with incident diabetes mellitus in community-living older adults: the cardiovascular health study.}, journal = {Circulation}, volume = {125}, year = {2012}, month = {2012 May 15}, pages = {2316-22}, abstract = {

BACKGROUND: The liver-secreted protein fetuin-A induces peripheral insulin resistance in vitro. In a pilot study, we observed that higher fetuin-A levels were associated with diabetes mellitus in older persons. However, this finding has not been confirmed in large cohorts. We sought to confirm the association of fetuin-A with incident diabetes mellitus in older persons and to determine whether the association differs by age, sex, and race and among persons with cardiovascular disease (CVD).

METHODS AND RESULTS: Among 3710 community-living individuals >= 65 years of age without diabetes mellitus at baseline, fetuin-A was measured in serum collected in 1992 to 1993. Participants were followed up for 10.6 years (median) for incident diabetes mellitus. Cox regression models evaluated the association of fetuin-A with incident diabetes mellitus. Interaction terms evaluated heterogeneity by age, sex, race, and CVD. Mean age was 75 years; 60 were female; 15 were black; and 16 had CVD. Mean fetuin-A concentrations were 0.47 {\textpm} 0.10 g/L. During follow-up, 305 incident diabetes cases occurred. Each 0.10-g/L (SD)-greater fetuin-A was associated with 19 higher risk of diabetes mellitus (hazard ratio, 1.19; 95 confidence interval, 1.06-1.33) after adjustment for demographics, lifestyle factors, albumin, kidney function, and CVD. Further adjustment for potential mediators (body mass index, waist circumference, hypertension, lipids, and C-reactive protein) moderately attenuated the association (hazard ratio, 1.13; 95 confidence interval, 1.00-1.28). Results were similar by sex, race, and CVD status but were stronger in persons <75 years old (P for interaction=0.01).

CONCLUSIONS: Higher fetuin-A is associated with incident diabetes mellitus in older persons regardless of sex, race, or prevalent CVD status. The association may be attenuated in those >= 75 years of age.

}, keywords = {African Continental Ancestry Group, Age Distribution, Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Body Mass Index, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Humans, Incidence, Life Style, Lipids, Male, Pilot Projects, Prevalence, Proportional Hazards Models, Residence Characteristics, Risk Factors, Sex Distribution}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.111.072751}, author = {Ix, Joachim H and Biggs, Mary L and Mukamal, Kenneth J and Kizer, Jorge R and Zieman, Susan J and Siscovick, David S and Mozzaffarian, Dariush and Jensen, Majken K and Nelson, Lauren and Ruderman, Neil and Djouss{\'e}, Luc} } @article {1406, title = {Association of mild to moderate chronic kidney disease with venous thromboembolism: pooled analysis of five prospective general population cohorts.}, journal = {Circulation}, volume = {126}, year = {2012}, month = {2012 Oct 16}, pages = {1964-71}, abstract = {

BACKGROUND: Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted.

METHODS AND RESULTS: We pooled individual participant data from 5 community-based cohorts from Europe (second Nord-Tr{\o}ndelag Health Study [HUNT2], Prevention of Renal and Vascular End-stage Disease [PREVEND], and the Troms{\o} study) and the United States (Atherosclerosis Risks in Communities [ARIC] and Cardiovascular Health Study [CHS]) to assess the association of estimated glomerular filtration rate (eGFR), albuminuria, and CKD with objectively verified VTE. To estimate adjusted hazard ratios for VTE, categorical and continuous spline models were fit by using Cox regression with shared-frailty or random-effect meta-analysis. A total of 1178 VTE events occurred over 599 453 person-years follow-up. Relative to eGFR 100 mL/min per 1.73 m(2), hazard ratios for VTE were 1.29 (95\% confidence interval, 1.04-1.59) for eGFR 75, 1.31 (1.00-1.71) for eGFR 60, 1.82 (1.27-2.60) for eGFR 45, and 1.95 (1.26-3.01) for eGFR 30 mL/min per 1.73 m(2). In comparison with an albumin-to-creatinine ratio (ACR) of 5.0 mg/g, the hazard ratios for VTE were 1.34 (1.04-1.72) for ACR 30 mg/g, 1.60 (1.08-2.36) for ACR 300 mg/g, and 1.92 (1.19-3.09) for ACR 1000 mg/g. There was no interaction between clinical categories of eGFR and ACR (P=0.20). The adjusted hazard ratio for CKD, defined as eGFR <60 mL/min per 1.73 m(2) or albuminuria >=30 mg/g, (versus no CKD) was 1.54 (95\% confidence interval, 1.15-2.06). Associations were consistent in subgroups according to age, sex, and comorbidities, and for unprovoked versus provoked VTE, as well.

CONCLUSIONS: Both eGFR and ACR are independently associated with increased risk of VTE in the general population, even across the normal eGFR and ACR ranges.

}, keywords = {Aged, Cohort Studies, Europe, Female, Humans, Incidence, Male, Middle Aged, Prevalence, Renal Insufficiency, Chronic, Risk Factors, Severity of Illness Index, Venous Thromboembolism}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.113944}, author = {Mahmoodi, Bakhtawar K and Gansevoort, Ron T and N{\ae}ss, Inger Anne and Lutsey, Pamela L and Br{\ae}kkan, Sigrid K and Veeger, Nic J G M and Brodin, Ellen E and Meijer, Karina and Sang, Yingying and Matsushita, Kunihiro and Hallan, Stein I and Hammerstr{\o}m, Jens and Cannegieter, Suzanne C and Astor, Brad C and Coresh, Josef and Folsom, Aaron R and Hansen, John-Bjarne and Cushman, Mary} } @article {1362, title = {Association of plasma phospholipid long-chain ω-3 fatty acids with incident atrial fibrillation in older adults: the cardiovascular health study.}, journal = {Circulation}, volume = {125}, year = {2012}, month = {2012 Mar 06}, pages = {1084-93}, abstract = {

BACKGROUND: Experimental studies suggest that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) may reduce the risk of atrial fibrillation (AF). Prior studies evaluating fish or n-3 PUFA consumption from dietary questionnaires and incident AF have been conflicting. Circulating levels of n-3 PUFAs provide an objective measurement of exposure.

METHODS AND RESULTS: Among 3326 US men and women >=65 years of age and free of AF or heart failure at baseline, plasma phospholipid levels of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were measured at baseline by use of standardized methods. Incident AF (789 cases) was identified prospectively from hospital discharge records and study visit ECGs during 31 169 person-years of follow-up (1992-2006). In multivariable Cox models adjusted for other risk factors, the relative risk in the top versus lowest quartile of total n-3 PUFAs (eicosapentaenoic acid+docosapentaenoic acid+docosahexaenoic acid) levels was 0.71 (95\% confidence interval, 0.57-0.89; P for trend=0.004) and of DHA levels was 0.77 (95\% confidence interval, 0.62-0.96; P for trend=0.01). Eicosapentaenoic acid and docosapentaenoic acid levels were not significantly associated with incident AF. Evaluated nonparametrically, both total n-3 PUFAs and docosahexaenoic acid showed graded and linear inverse associations with incidence of AF. Adjustment for intervening events such as heart failure or myocardial infarction during follow-up did not appreciably alter results.

CONCLUSIONS: In older adults, higher circulating total long-chain n-3 PUFA and docosahexaenoic acid levels were associated with lower risk of incident AF. These results highlight the need to evaluate whether increased dietary intake of these fatty acids could be effective for the primary prevention of AF.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, Dietary Fats, Docosahexaenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Female, Follow-Up Studies, Humans, Incidence, Male, Proportional Hazards Models, Risk Factors, Seafood}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.111.062653}, author = {Wu, Jason H Y and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Sacks, Frank M and Rimm, Eric B and Heckbert, Susan R and Siscovick, David S and Mozaffarian, Dariush} } @article {1368, title = {Chronic kidney disease, insulin resistance, and incident diabetes in older adults.}, journal = {Clin J Am Soc Nephrol}, volume = {7}, year = {2012}, month = {2012 Apr}, pages = {588-94}, abstract = {

BACKGROUND AND OBJECTIVES: Insulin resistance is a complication of advanced CKD. Insulin resistance is less well characterized in earlier stages of CKD. The response of the pancreatic β cell, effects on glucose tolerance, and risk of diabetes are not clear.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: The Cardiovascular Health Study included 4680 adults without baseline diabetes. The Chronic Kidney Disease Epidemiology Collaboration creatinine equation was used to obtain the estimated GFR (eGFR). Insulin resistance was evaluated as fasting insulin concentration. The insulin sensitivity index, β cell function, and glucose tolerance were assessed by oral glucose tolerance testing. Incident diabetes was defined as fasting glucose >=126 mg/dl, nonfasting glucose >=200 mg/dl, or use of glucose-lowering medications.

RESULTS: Mean age was 72.5 years (range, 65-98 years). Mean eGFR was 72.2 (SD 17.1) ml/min per 1.73 m(2). After adjustment, each 10 ml/min per 1.73 m(2) lower eGFR was associated with a 2.2\% higher fasting insulin concentration (95\% confidence interval [CI], 1.4\%, 2.9\%; P<0.001) and a 1.1\% lower insulin sensitivity index (95\% CI, 0.03\%, 2.2\%; P=0.04). Surprisingly, eGFR was associated with an augmented β cell function index (P<0.001), lower 2-hour glucose concentration (P=0.002), and decreased risk of glucose intolerance (P=0.006). Over a median 12 years{\textquoteright} follow-up, 437 participants (9.3\%) developed diabetes. eGFR was not associated with the risk of incident diabetes.

CONCLUSIONS: Among older adults, lower eGFR was associated with insulin resistance. However, with lower eGFR, β cell function was appropriately augmented and risks of impaired glucose tolerance and incident diabetes were not increased.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Biomarkers, Chronic Disease, Creatinine, Diabetes Mellitus, Female, Glomerular Filtration Rate, Glucose Tolerance Test, Health Surveys, Humans, Hypoglycemic Agents, Incidence, Insulin, Insulin Resistance, Insulin-Secreting Cells, Kidney, Kidney Diseases, Linear Models, Male, Proportional Hazards Models, Risk Assessment, Risk Factors, United States}, issn = {1555-905X}, doi = {10.2215/CJN.11861111}, author = {Pham, Hien and Robinson-Cohen, Cassianne and Biggs, Mary L and Ix, Joachim H and Mukamal, Kenneth J and Fried, Linda F and Kestenbaum, Bryan and Siscovick, David S and de Boer, Ian H} } @article {1396, title = {Circulating and dietary α-linolenic acid and incidence of congestive heart failure in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {96}, year = {2012}, month = {2012 Aug}, pages = {269-74}, abstract = {

BACKGROUND: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF).

OBJECTIVE: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF.

DESIGN: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged >=65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression.

RESULTS: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95\% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95\% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535).

CONCLUSION: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

}, keywords = {Aged, Alcohol Drinking, alpha-Linolenic Acid, Biomarkers, Body Mass Index, Cardiovascular Diseases, Diet, Fatty Acid Desaturases, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Risk Factors, Smoking, Surveys and Questionnaires, United States}, issn = {1938-3207}, doi = {10.3945/ajcn.112.037960}, author = {Lemaitre, Rozenn N and Sitlani, Colleen and Song, Xiaoling and King, Irena B and McKnight, Barbara and Spiegelman, Donna and Sacks, Frank M and Djouss{\'e}, Luc and Rimm, Eric B and Siscovick, David S and Mozaffarian, Dariush} } @article {1408, title = {Development and validation of a coronary risk prediction model for older U.S. and European persons in the Cardiovascular Health Study and the Rotterdam Study.}, journal = {Ann Intern Med}, volume = {157}, year = {2012}, month = {2012 Sep 18}, pages = {389-97}, abstract = {

BACKGROUND: Risk scores for prediction of coronary heart disease (CHD) in older adults are needed.

OBJECTIVE: To develop a sex-specific CHD risk prediction model for older adults that accounts for competing risks for death.

DESIGN: 2 observational cohort studies, using data from 4946 participants in the Cardiovascular Health Study (CHS) and 4303 participants in the Rotterdam Study (RS).

SETTING: Community settings in the United States (CHS) and Rotterdam, the Netherlands (RS).

PARTICIPANTS: Persons aged 65 years or older who were free of cardiovascular disease.

MEASUREMENTS: A composite of nonfatal myocardial infarction and coronary death.

RESULTS: During a median follow-up of 16.5 and 14.9 years, 1166 CHS and 698 RS participants had CHD events, respectively. Deaths from noncoronary causes largely exceeded the number of CHD events, complicating accurate CHD risk predictions. The prediction model had moderate ability to discriminate between events and nonevents (c-statistic, 0.63 in both U.S. and European men and 0.67 and 0.68 in U.S. and European women). The model was well-calibrated; predicted risks were in good agreement with observed risks. Compared with the Framingham point scores, the prediction model classified elderly U.S. persons into higher risk categories but elderly European persons into lower risk categories. Differences in classification accuracy were not consistent and depended on cohort and sex. Adding newer cardiovascular risk markers to the model did not substantially improve performance.

LIMITATION: The model may be less applicable in nonwhite populations, and the comparison Framingham model was not designed for adults older than 79 years.

CONCLUSION: A CHD risk prediction model that accounts for deaths from noncoronary causes among older adults provided well-calibrated risk estimates but was not substantially more accurate than Framingham point scores. Moreover, adding newer risk markers did not improve accuracy. These findings emphasize the difficulties of predicting CHD risk in elderly persons and the need to improve these predictions.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; The Netherlands Organisation for Scientific Research; and the Netherlands Organisation for Health Research and Development.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Cause of Death, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Male, Models, Statistical, Multivariate Analysis, Netherlands, Prospective Studies, Risk Assessment, Risk Factors, United States}, issn = {1539-3704}, doi = {10.7326/0003-4819-157-6-201209180-00002}, author = {Koller, Michael T and Leening, Maarten J G and Wolbers, Marcel and Steyerberg, Ewout W and Hunink, M G Myriam and Schoop, Rotraut and Hofman, Albert and Bucher, Heiner C and Psaty, Bruce M and Lloyd-Jones, Donald M and Witteman, Jacqueline C M} } @article {1364, title = {Genetic variation in F3 (tissue factor) and the risk of incident venous thrombosis: meta-analysis of eight studies.}, journal = {J Thromb Haemost}, volume = {10}, year = {2012}, month = {2012 Apr}, pages = {719-22}, keywords = {Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Humans, Incidence, Male, Middle Aged, Phenotype, Regression Analysis, Risk Assessment, Risk Factors, Thromboplastin, Venous Thrombosis}, issn = {1538-7836}, doi = {10.1111/j.1538-7836.2012.04665.x}, author = {Smith, N L and Heit, J A and Tang, W and Teichert, M and Chasman, D I and Morange, P-E} } @article {1557, title = {Incidence of mild cognitive impairment in the Pittsburgh Cardiovascular Health Study-Cognition Study.}, journal = {Neurology}, volume = {79}, year = {2012}, month = {2012 Oct 09}, pages = {1599-606}, abstract = {

OBJECTIVES AND METHODS: The purpose of this study was to examine the incidence of mild cognitive impairment (MCI) and patterns of progression from incident MCI to dementia in 285 cognitively normal subjects (mean age, 78.9 years) in the Cardiovascular Health Study-Cognition Study from 1998-1999 to 2010-2011.

RESULTS: Two hundred (70\%) of the participants progressed to MCI; the age-adjusted incidence of MCI was 111.09 (95\% confidence interval, 88.13-142.95) per 1,000 person-years. A total of 107 (53.5\%) of the incident MCI subjects progressed to dementia. The mean time from MCI to dementia was 2.8 {\textpm} 1.8 years. Forty (20\%) of the incident MCI cases had an "unstable" course: 19 (9.5\%) converted to MCI and later returned to normal; 10 (5\%) converted to MCI, to normal, and later back to MCI; 7 (3.5\%) converted to MCI, to normal, to MCI, and later to dementia; and 4 (2\%) converted to MCI, to normal, and later to dementia. There was an increased mortality rate among the cognitively normal group (110.10 per 1,000 person-years) compared to those with incident MCI who converted to dementia (41.32 per 1,000 person-years).

CONCLUSIONS: The majority of the subjects aged >80 years developed an MCI syndrome, and half of them progressed to dementia. Once the MCI syndrome was present, the symptoms of dementia appeared within 2 to 3 years. Progression from normal to MCI or from normal to MCI to dementia is not always linear; subjects who developed MCI and later returned to normal can subsequently progress to dementia. Competing mortality and morbidity influence the study of incident MCI and dementia in population cohorts.

}, keywords = {Aged, Aged, 80 and over, Cognitive Dysfunction, Dementia, Disease Progression, Female, Health Surveys, Humans, Incidence, Male, Risk Factors, Severity of Illness Index}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31826e25f0}, author = {Lopez, Oscar L and Becker, James T and Chang, Yue-Fang and Sweet, Robert A and DeKosky, Steven T and Gach, Michael H and Carmichael, Owen T and McDade, Eric and Kuller, Lewis H} } @article {1370, title = {Insulin resistance and incident peripheral artery disease in the Cardiovascular Health Study.}, journal = {Vasc Med}, volume = {17}, year = {2012}, month = {2012 Apr}, pages = {85-93}, abstract = {

Type 2 diabetes is a risk factor for peripheral artery disease (PAD), and insulin resistance is a key feature of diabetes and pre-diabetes. No longitudinal epidemiological study has examined the relation between insulin resistance and PAD. Our study analyzed the association of quartiles of the homeostatic model of insulin resistance (HOMA-IR) and the development of PAD defined by two methods. PAD was first defined as the development of an abnormal ankle-brachial index (ABI) (dichotomous outcome) after 6 years of follow-up. PAD was alternatively defined as the development of clinical PAD (time-to-event analysis). The study samples included adults over the age of 65 years who were enrolled in the Cardiovascular Health Study, had fasting measurements of insulin and glucose, had ABI measurements, and were not receiving treatment for diabetes. Multivariable models were adjusted for potential confounders, including age, sex, field center and cohort, body mass index (BMI), smoking status, alcohol use, and exercise intensity. Additional models adjusted for potential mediators, including blood pressure, lipids, kidney function, and prevalent vascular disease. In the ABI analysis (n = 2108), multivariable adjusted models demonstrated a positive relation between HOMA-IR and incident PAD (odds ratio = 1.80 comparing the 4th versus 1st quartile of HOMA-IR, 95\% confidence interval [CI] 1.20-2.71). In the clinical PAD analysis (n = 4208), we found a similar relation (hazard ratio = 2.30 comparing the 4th versus 1st quartile of HOMA-IR, 95\% CI 1.15-4.58). As expected, further adjustment for potential mediators led to some attenuation of effect estimates. In conclusion, insulin resistance is associated with a higher risk of PAD in older adults.

}, keywords = {Aged, Ankle Brachial Index, Biomarkers, Blood Glucose, Diabetes Mellitus, Type 2, Diabetic Angiopathies, Fasting, Female, Health Surveys, Humans, Incidence, Insulin, Insulin Resistance, Logistic Models, Longitudinal Studies, Male, Odds Ratio, Peripheral Arterial Disease, Predictive Value of Tests, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1477-0377}, doi = {10.1177/1358863X11436195}, author = {Britton, Kathryn A and Mukamal, Kenneth J and Ix, Joachim H and Siscovick, David S and Newman, Anne B and de Boer, Ian H and Thacker, Evan L and Biggs, Mary L and Gaziano, J Michael and Djouss{\'e}, Luc} } @article {1369, title = {Lipoprotein-associated phospholipase A2 (Lp-PLA2) and future risk of type 2 diabetes: results from the Cardiovascular Health Study.}, journal = {J Clin Endocrinol Metab}, volume = {97}, year = {2012}, month = {2012 May}, pages = {1695-701}, abstract = {

INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) has been consistently associated with cardiovascular disease (CVD) risk factors and predictive of CVD outcomes; furthermore, it is consistently higher among type 2 diabetics than nondiabetics. However, the relationships of circulating Lp-PLA(2) mass and activity with incident type 2 diabetes mellitus have not been examined. Therefore, the purpose of this study was to determine the association of Lp-PLA(2) mass and activity with type 2 diabetes among older adults.

METHODS: We conducted analyses of Lp-PLA(2) and prevalent and incident diabetes among 5474 men and women from the Cardiovascular Health Study (1989-2007). Lp-PLA(2) mass and activity were measured in baseline plasma. Diabetes status was ascertained annually with medication inventories and repeated blood glucose measurements. Generalized linear and Cox proportional hazards models were used to adjust for confounding factors including body mass index and inflammation.

RESULTS: At baseline, the top two quintiles of Lp-PLA(2) activity were significantly associated with prevalent type 2 diabetes with a multivariable relative risk = 1.35 [95\% confidence interval (CI) = 1.11-1.63] for quintile 4, and relative risk = 1.33 (95\% CI = 1.07-1.66) for quintile 5. Among participants free of diabetes at baseline, we found a significant positive association with both the homeostatic model assessment for insulin resistance and β-cell function per SD increase in Lp-PLA(2) activity (P values for both <0.01). In prospective analyses, the risk of incident type 2 diabetes was significantly higher among those in the highest quintile of Lp-PLA(2) activity [multivariable hazard ratio = 1.45 (95\% CI = 1.01-2.07)] compared with the lowest quintile. Lp-PLA(2) mass was not significantly associated with incident type 2 diabetes.

DISCUSSION: Lp-PLA(2) activity is positively associated with insulin resistance and predicts incident type 2 diabetes among older adults independent of multiple factors associated with diabetes pathogenesis.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Aged, Aged, 80 and over, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Insulin Resistance, Male, Middle Aged, Predictive Value of Tests, Prevalence, Prospective Studies, Risk, Risk Factors}, issn = {1945-7197}, doi = {10.1210/jc.2011-3026}, author = {Nelson, T L and Biggs, M L and Kizer, J R and Cushman, M and Hokanson, J E and Furberg, C D and Mukamal, K J} } @article {1354, title = {Markers of inflammation in prevalent and incident Parkinson{\textquoteright}s disease in the Cardiovascular Health Study.}, journal = {Parkinsonism Relat Disord}, volume = {18}, year = {2012}, month = {2012 Mar}, pages = {274-8}, abstract = {

BACKGROUND: Studies demonstrate existence of inflammation in prevalent Parkinson{\textquoteright}s disease (PD). We assessed associations of baseline levels of inflammatory markers with prevalent PD at baseline (1989) and incident PD identified over 13 years of follow-up of the Cardiovascular Health Study.

METHODS: Blood samples at baseline were measured for fibrinogen, interleukin-6, tumor necrosis factor-α, C-reactive protein, albumin, and white blood cells. The analysis included 60 prevalent and 154 incident PD cases.

RESULTS: Risk of prevalent PD was significantly higher per doubling of IL-6 among women (odds ratio [OR]=1.5, 95\% confidence interval [CI]: 1.0, 2.4) and WBC among men (OR: 2.4, 95\% CI: 1.2, 4.9) in multivariate models. Risk of incident PD was not associated with higher levels of any biomarker after adjusting for age, smoking, African American race, and history of diabetes. Inverse associations with incident PD were observed per doubling of C-reactive protein (OR=0.9; 95\% CI: 0.8, 1.0) and of fibrinogen among women (OR=0.4; 95\% CI: 0.2, 0.8).

CONCLUSIONS: Although inflammation exists in PD, it may not represent an etiologic factor. Our findings suggest the need for larger studies that measure inflammatory markers before PD onset.

}, keywords = {Aged, Aged, 80 and over, Albumins, Biomarkers, C-Reactive Protein, Enzyme-Linked Immunosorbent Assay, Female, Fibrinogen, Humans, Incidence, Inflammation, Interleukin-6, Leukocyte Count, Male, Parkinson Disease, Prevalence, Risk Factors, Tumor Necrosis Factor-alpha}, issn = {1873-5126}, doi = {10.1016/j.parkreldis.2011.11.003}, author = {Ton, Thanh G N and Jain, Samay and Biggs, Mary L and Thacker, Evan L and Strotmeyer, Elsa S and Boudreau, Robert and Newman, Anne B and Longstreth, W T and Checkoway, Harvey} } @article {1361, title = {Nonesterified fatty acids and risk of sudden cardiac death in older adults.}, journal = {Circ Arrhythm Electrophysiol}, volume = {5}, year = {2012}, month = {2012 Apr}, pages = {273-8}, abstract = {

BACKGROUND: Although nonesterified fatty acids (NEFA) have been positively associated with coronary heart disease risk factors, limited and inconsistent data are available on the relation between NEFA and sudden cardiac death.

METHODS AND RESULTS: Using a prospective design, we studied 4657 older men and women (mean age, 75 years) from the Cardiovascular Health Study (1992-2006) to evaluate the association between plasma NEFA and the risk of sudden cardiac death in older adults. Plasma concentrations of NEFA were measured using established enzymatic methods, and sudden death was adjudicated using medical records, death certificates, proxy interview, and autopsy reports. We used Cox proportional hazard models to estimate multivariable-adjusted relative risks. During a median follow-up of 10.0 years, 221 new cases of sudden cardiac death occurred. In a multivariable model adjusting for age, sex, race, clinic site, alcohol intake, smoking, prevalent coronary heart disease and heart failure, and self-reported health status, relative risks (95\% confidence interval) for sudden cardiac death were 1.0 (ref), 1.15 (0.81-1.64), 1.06 (0.72-1.55), and 0.91 (0.60-1.38) across consecutive quartiles of NEFA concentration. In secondary analyses restricted to the first 5 years of follow-up, we also did not observe a statistically significant association between plasma NEFA and sudden cardiac death.

CONCLUSIONS: Our data do not provide evidence for an association between plasma NEFA measured late in life and the risk of sudden cardiac death in older adults.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Death, Sudden, Cardiac, Fatty Acids, Nonesterified, Female, Follow-Up Studies, Humans, Incidence, Male, Proportional Hazards Models, Prospective Studies, Retrospective Studies, Risk Factors}, issn = {1941-3084}, doi = {10.1161/CIRCEP.111.967661}, author = {Djouss{\'e}, Luc and Biggs, Mary L and Ix, Joachim H and Kizer, Jorge R and Lemaitre, Rozenn N and Sotoodehnia, Nona and Zieman, Susan J and Mozaffarian, Dariush and Tracy, Russell P and Mukamal, Kenneth J and Siscovick, David S} } @article {1410, title = {Novel circulating fatty acid patterns and risk of cardiovascular disease: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {96}, year = {2012}, month = {2012 Dec}, pages = {1252-61}, abstract = {

BACKGROUND: Complex interplays of diet and metabolism influence circulating fatty acids (FAs), possibly constituting FA patterns related to cardiovascular disease (CVD) risk.

OBJECTIVES: We aimed to derive FA patterns from circulating FAs, relate the patterns to CVD incidence, and extend the derived patterns to atherosclerosis progression in another independent cohort.

DESIGN: We used principal component analysis (PCA) to derive FA patterns from 38 plasma phospholipid FAs in 2972 older adults in the Cardiovascular Health Study (CHS). Identified patterns were evaluated for prospective associations with 14-y incidence of CVD [ischemic heart disease (IHD) or stroke]. In another independent cohort of postmenopausal women with IHD, we evaluated associations of the CHS-derived patterns with 3.2-y progression of angiographically defined coronary atherosclerosis.

RESULTS: Three distinct patterns were identified, characterized by higher proportions of trans FAs, de novo lipogenesis (DNL) FAs, and long-chain MUFAs (LCMUFAs). During 32,265 person-years, 780 incident CVD events occurred. The trans FA pattern was associated with higher CVD risk (multivariable-adjusted HR for the highest compared with the lowest quintiles = 1.58; 95\% CI: 1.17, 2.12; P-trend = 0.006), primarily attributable to higher risk of stroke (HR: 2.46; 95\% CI: 1.54, 3.92; P-trend = 0.005). The DNL and LCMUFA patterns were not associated with CVD incidence or with IHD or stroke (P-trend > 0.11 each). In the second cohort, the trans FA pattern, but not the other 2 patterns, was positively associated with progression of coronary atherosclerosis (P-trend < 0.05).

CONCLUSIONS: PCA appears to provide informative circulating FA patterns. A pattern driven mainly by trans FA levels related to greater CVD risk in older adults and coronary atherosclerosis progression in women with IHD.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cohort Studies, Coronary Artery Disease, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Myocardial Ischemia, Principal Component Analysis, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, Trans Fatty Acids, United States}, issn = {1938-3207}, doi = {10.3945/ajcn.112.039990}, author = {Imamura, Fumiaki and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Lichtenstein, Alice H and Matthan, Nirupa R and Herrington, David M and Siscovick, David S and Mozaffarian, Dariush} } @article {1379, title = {Plasma free fatty acids and risk of atrial fibrillation (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {110}, year = {2012}, month = {2012 Jul 15}, pages = {212-6}, abstract = {

Atrial fibrillation (AF) is a highly prevalent cardiac arrhythmia in clinical practice, affecting approximately 2.3 million residents of the United States and 4.5 million residents of the European Union. It is unclear whether plasma free fatty acids (FFAs) influence the risk of AF in older adults. The aim of this study was to prospectively examine the association between plasma FFAs and incident AF in a prospective cohort of 4,175 men and women >=65 years old from the Cardiovascular Health Study. Plasma concentrations of FFAs were measured 2 times during the 1992 to 1993 examination. Incident AF was ascertained based on study electrocardiographic and hospitalization records during follow-up. We used Cox regression to estimate relative risks of AF. Average age at baseline was 74.6 {\textpm} 5.1 years. During a mean follow-up of 10.0 years, 1,041 new cases of AF occurred. Crude incidence rates of AF were 23.7, 23.3, 23.9, and 29.7 cases/1,000 person-years across consecutive quartiles of plasma FFAs. There was a positive association between plasma FFAs and risk of AF. Multivariable adjusted hazard ratios (95\% confidence intervals) for incident AF were 1.00 (referent), 1.02 (0.85 to 1.21), 1.05 (0.88 to 1.26), and 1.29 (1.08 to 1.55) from the lowest to highest quartiles of FFAs, respectively. In a secondary analysis restricted to the first 5 years of follow-up, this association persisted. In conclusion, our data show an increased risk of AF with higher plasma FFAs in community-dwelling older adults.

}, keywords = {Aged, Atrial Fibrillation, C-Reactive Protein, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Follow-Up Studies, Humans, Hypertension, Incidence, Lipoproteins, HDL, Lipoproteins, LDL, Male, Natriuretic Peptide, Brain, Obesity, Peptide Fragments, Prospective Studies, Sex Factors, Triglycerides, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2012.03.010}, author = {Khawaja, Owais and Bartz, Traci M and Ix, Joachim H and Heckbert, Susan R and Kizer, Jorge R and Zieman, Susan J and Mukamal, Kenneth J and Tracy, Russell P and Siscovick, David S and Djouss{\'e}, Luc} } @article {1351, title = {Retinal microvascular signs and disability in the Cardiovascular Health Study.}, journal = {Arch Ophthalmol}, volume = {130}, year = {2012}, month = {2012 Mar}, pages = {350-6}, abstract = {

OBJECTIVE: To study the associations of retinal microvascular changes, which are associated with systemic conditions and cognitive decline, with disability in performing activities of daily living (ADL).

DESIGN: Prospective cohort study of 1487 community-dwelling participants in the Cardiovascular Health Study (mean age, 78 years) who were free of ADL disability and had available data on retinal signs and carotid intima-media thickness at the 1998-1999 visit. Main outcome measures were incident ADL disability, defined as self-reported difficulty in performing any ADL, by the presence of retinal signs and advanced carotid atherosclerosis, defined by carotid intima-media thickness in the 80th percentile or more or 25\% or more stenosis, and potential mediation by cerebral microvascular disease on brain imaging or by executive dysfunction, slow gait, and depressive mood, which are symptoms of frontal subcortical dysfunction.

RESULTS: During the median follow-up of 3.1 years (maximum, 7.8 years), participants with 2 or more retinal signs had a higher rate of disability than those with fewer than 2 retinal signs (10.1\% vs 7.1\%; adjusted hazard ratio, 1.45; 95\% confidence interval, 1.24-1.69; P~<~.001). There was no evidence of interaction by advanced carotid atherosclerosis (P~>~.10). The association seemed to be partially mediated by executive dysfunction, slow gait, and depressive symptoms but not by cerebral microvascular disease on brain imaging.

CONCLUSIONS: These results provide further support for the pathophysiologic and prognostic significance of microvascular disease in age-related disability. However, it remains to be determined how to best use retinal photography in clinical risk prediction.

}, keywords = {Activities of Daily Living, Aged, Carotid Artery Diseases, Cognition Disorders, Diagnostic Techniques, Ophthalmological, Disability Evaluation, Follow-Up Studies, Humans, Hypertension, Incidence, Kaplan-Meier Estimate, Microcirculation, Predictive Value of Tests, Prevalence, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Smoking}, issn = {1538-3601}, doi = {10.1001/archophthalmol.2011.360}, author = {Kim, Dae Hyun and Chaves, Paulo H M and Newman, Anne B and Klein, Ronald and Sarnak, Mark J and Newton, Elizabeth and Strotmeyer, Elsa S and Burke, Gregory L and Lipsitz, Lewis A} } @article {1381, title = {Risk of intraparenchymal hemorrhage with magnetic resonance imaging-defined leukoaraiosis and brain infarcts.}, journal = {Ann Neurol}, volume = {71}, year = {2012}, month = {2012 Apr}, pages = {552-9}, abstract = {

OBJECTIVE: To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by magnetic resonance imaging (MRI), are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population-based study.

METHODS: Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, we assessed white matter grade (range, 0-9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow-up, 71 incident, spontaneous IPH events occurred.

RESULTS: After adjustment for other IPH risk factors, the hazard ratios (95\% confidence intervals) across white matter grades 0 to 1, 2, 3, and 4 to 9 were 1.00, 1.68 (0.86-3.30), 3.52 (1.80-6.89), and 3.96 (1.90-8.27), respectively (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI-defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or >=3 MRI-defined brain infarcts were 1.00, 1.97 (1.10-3.54), 2.00 (0.83-4.78), and 3.12 (1.31-7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049).

INTERPRETATION: Greater MRI-defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis.

}, keywords = {Cerebral Infarction, Cohort Studies, Female, Humans, Incidence, Intracranial Hemorrhages, Leukoaraiosis, Magnetic Resonance Imaging, Male, Middle Aged, Risk Factors}, issn = {1531-8249}, doi = {10.1002/ana.22690}, author = {Folsom, Aaron R and Yatsuya, Hiroshi and Mosley, Thomas H and Psaty, Bruce M and Longstreth, W T} } @article {1403, title = {Transforming growth factor beta-1 and incidence of heart failure in older adults: the Cardiovascular Health Study.}, journal = {Cytokine}, volume = {60}, year = {2012}, month = {2012 Nov}, pages = {341-5}, abstract = {

CONTEXT: Transforming growth factor-beta1 (TGF-B1) is a highly pleiotropic cytokine whose functions include a central role in the induction of fibrosis.

OBJECTIVE: To investigate the hypothesis that elevated plasma levels of TGF-B1 are positively associated with incident heart failure (HF).

PARTICIPANTS AND METHODS: The hypotheses were tested using a two-phase case-control study design, ancillary to the Cardiovascular Health Study - a longitudinal, population-based cohort study. Cases were defined as having an incident HF event after their 1992-1993 exam and controls were free of HF at follow-up. TGF-B1 was measured using plasma collected in 1992-1993 and data from 89 cases and 128 controls were used for analysis. The association between TGF-B1 and risk of HF was evaluated using the weighted likelihood method, and odds ratios (OR) for risk of HF were calculated for TGF-B1 as a continuous linear variable and across quartiles of TGF-B1.

RESULTS: The OR for HF was 1.88 (95\% confidence intervals [CI] 1.26-2.81) for each nanogram increase in TGF-B1, and the OR for the highest quartile (compared to the lowest) of TGF-B1 was 5.79 (95\% CI 1.65-20.34), after adjustment for age, sex, C-reactive protein, platelet count and digoxin use. Further adjustment with other covariates did not change the results.

CONCLUSIONS: Higher levels of plasma TGF-B1 were associated with an increased risk of incident heart failure among older adults. However, further study is needed in larger samples to confirm these findings.

}, keywords = {Aged, Case-Control Studies, Health, Heart Failure, Humans, Incidence, Transforming Growth Factor beta1, United States}, issn = {1096-0023}, doi = {10.1016/j.cyto.2012.07.013}, author = {Glazer, Nicole L and Macy, Elizabeth M and Lumley, Thomas and Smith, Nicholas L and Reiner, Alex P and Psaty, Bruce M and King, George L and Tracy, Russell P and Siscovick, David S} } @article {6059, title = {Albuminuria is associated with hip fracture risk in older adults: the cardiovascular health study.}, journal = {Osteoporos Int}, volume = {24}, year = {2013}, month = {2013 Dec}, pages = {2993-3000}, abstract = {

UNLABELLED: The microcirculation plays an important role in bone health. Here, we examine whether albuminuria, a marker of renal microvascular disease, is associated with the risk of hip fracture in older adults (age, 78~years). We find a small independent association in women but not in men.

INTRODUCTION: The microvascular circulation plays an important role in bone physiology. Two studies of middle-aged adults have found that albuminuria (>30~mg albumin/g creatinine), a disorder of the renal microvasculature, is associated with fracture risk. Here, we examine whether albuminuria is related to hip fracture risk and reduced hip bone mineral density (BMD) in older adults with a mean age of 78~years.

METHODS: From the Cardiovascular Health Study (41~\% male), 3,110 adults with albuminuria testing were followed up for incident hip fracture for up to 9.5~years. BMD was performed in a subset of 1,208 participants.

RESULTS: There were 313 hip fractures during follow-up (7.7~\% of men; 11.7~\% of women). The incidence rate for men, with and without albuminuria, was 1.43 and 0.93/100 person-years of follow-up (p = 0.02); for women, 1.84 and 1.33 (p = 0.04). After adjustment for osteoporosis-related factors, frailty and falling, a doubling of albuminuria was significantly associated with hip fracture risk in women (hazard ratio, 1.12, 95~\% CI, 1.001-1.25), but not in men. In the subcohort with BMD measurement, increased urine albumin levels were significantly associated with decreased total hip BMD in men (-0.009~g calcium/cm(2) (-0.017, -0.001); p = 0.04), but not in women.

CONCLUSIONS: In older women, albuminuria is associated with a small, but statistically significant, increased risk of hip fracture independent of other explanatory factors. No such risk appears to be present in men, although their total hip BMD is lower in association with albuminuria.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Bone Density, Female, Follow-Up Studies, Hip Fractures, Hip Joint, Humans, Incidence, Kaplan-Meier Estimate, Male, Osteoporotic Fractures, Risk Factors, Sex Factors, United States}, issn = {1433-2965}, doi = {10.1007/s00198-013-2389-3}, author = {Barzilay, J I and B{\r u}{\v z}kov{\'a}, P and Chen, Z and de Boer, I H and Carbone, L and Rassouli, N N and Fink, H A and Robbins, J A} } @article {5846, title = {Associations of plasma phospholipid and dietary alpha linolenic acid with incident atrial fibrillation in older adults: the Cardiovascular Health Study.}, journal = {J Am Heart Assoc}, volume = {2}, year = {2013}, month = {2013 Jan 31}, pages = {e003814}, abstract = {

BACKGROUND: Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF).

METHODS AND RESULTS: The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95\% CI, 0.90 to 1.37), 1.09 (95\% CI, 0.88 to 1.35), and 0.92 (95\% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar.

CONCLUSIONS: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.

}, keywords = {Age Factors, Aged, Aged, 80 and over, alpha-Linolenic Acid, Atrial Fibrillation, Biomarkers, Diet, Female, Humans, Incidence, Linear Models, Longitudinal Studies, Male, Nutritional Status, Phospholipids, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.112.003814}, author = {Fretts, Amanda M and Mozaffarian, Dariush and Siscovick, David S and Heckbert, Susan R and McKnight, Barbara and King, Irena B and Rimm, Eric B and Psaty, Bruce M and Sacks, Frank M and Song, Xiaoling and Spiegelman, Donna and Lemaitre, Rozenn N} } @article {6002, title = {Atrial fibrillation and cognitive decline: a longitudinal cohort study.}, journal = {Neurology}, volume = {81}, year = {2013}, month = {2013 Jul 09}, pages = {119-25}, abstract = {

OBJECTIVE: We sought to determine whether in the absence of clinical stroke, people with atrial fibrillation experience faster cognitive decline than people without atrial fibrillation.

METHODS: We conducted a longitudinal analysis in the Cardiovascular Health Study, a community-based study of 5,888 men and women aged 65 years and older, enrolled in 1989/1990 or 1992/1993. Participants did not have atrial fibrillation or a history of stroke at baseline. Participants were censored when they experienced incident clinical stroke. Incident atrial fibrillation was identified by hospital discharge diagnosis codes and annual study ECGs. The main outcome was rate of decline in mean scores on the 100-point Modified Mini-Mental State Examination (3MSE), administered annually up to 9 times.

RESULTS: Analyses included 5,150 participants, of whom 552 (10.7\%) developed incident atrial fibrillation during a mean of 7 years of follow-up. Mean 3MSE scores declined faster after incident atrial fibrillation compared with no prior atrial fibrillation. For example, the predicted 5-year decline in mean 3MSE score from age 80 to age 85 was -6.4 points (95\% confidence interval [CI]: -7.0, -5.9) for participants without a history of atrial fibrillation, but was -10.3 points (95\% CI: -11.8, -8.9) for participants experiencing incident atrial fibrillation at age 80, a 5-year difference of -3.9 points (95\% CI: -5.3, -2.5).

CONCLUSIONS: In the absence of clinical stroke, people with incident atrial fibrillation are likely to reach thresholds of cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cognition Disorders, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Luria-Nebraska Neuropsychological Battery, Male, Predictive Value of Tests}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31829a33d1}, author = {Thacker, Evan L and McKnight, Barbara and Psaty, Bruce M and Longstreth, W T and Sitlani, Colleen M and Dublin, Sascha and Arnold, Alice M and Fitzpatrick, Annette L and Gottesman, Rebecca F and Heckbert, Susan R} } @article {5850, title = {Atrial fibrillation and the risk of sudden cardiac death: the atherosclerosis risk in communities study and cardiovascular health study.}, journal = {JAMA Intern Med}, volume = {173}, year = {2013}, month = {2013 Jan 14}, pages = {29-35}, abstract = {

BACKGROUND: It is unknown whether atrial fibrillation (AF) is associated with an increased risk of sudden cardiac death (SCD) in the general population. This association was examined in 2 population-based cohorts.

METHODS: In the Atherosclerosis Risk in Communities (ARIC) Study, we analyzed data from 15 439 participants (baseline age, 45-64 years; 55.2\% women; and 26.6\% black) from baseline (1987-1989) through December 31, 2001. In the Cardiovascular Health Study (CHS), we analyzed data from 5479 participants (baseline age, >=65 years; 58.2\% women; and 15.4\% black) from baseline (first cohort, 1989-1990; second cohort, 1992-1993) through December 31, 2006. The main outcome was physician-adjudicated SCD, defined as death from a sudden, pulseless condition presumed to be due to a ventricular tachyarrhythmia. The secondary outcome was non-SCD (NSCD), defined as coronary heart disease death not meeting SCD criteria. We used Cox proportional hazards models to assess the association between AF and SCD/NSCD, adjusting for baseline demographic and cardiovascular risk factors.

RESULTS: In the ARIC Study, 894 AF, 269 SCD, and 233 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 2.89 per 1000 person-years (with AF) and 1.30 per 1000 person-years (without AF). The multivariable hazard ratios (HRs) (95\% CIs) of AF for SCD and NSCD were 3.26 (2.17-4.91) and 2.43 (1.60-3.71), respectively. In the CHS, 1458 AF, 292 SCD, and 581 NSCD events occurred during follow-up (median, 13.1 years). The crude incidence rates of SCD were 12.00 per 1000 person-years (with AF) and 3.82 per 1000 person-years (without AF). The multivariable HRs (95\% CIs) of AF for SCD and NSCD were 2.14 (1.60-2.87) and 3.10 (2.58-3.72), respectively. The meta-analyzed HRs (95\% CIs) of AF for SCD and NSCD were 2.47 (1.95-3.13) and 2.98 (2.52-3.53), respectively.

CONCLUSIONS: Incident AF is associated with an increased risk of SCD and NSCD in the general population. Additional research to identify predictors of SCD in patients with AF is warranted.

}, keywords = {Aged, Atrial Fibrillation, Cardiovascular Diseases, Death, Sudden, Cardiac, Demography, Ethnic Groups, Female, Humans, Incidence, Male, Middle Aged, Proportional Hazards Models, Risk Assessment, Risk Factors, Sex Factors, United States}, issn = {2168-6114}, doi = {10.1001/2013.jamainternmed.744}, author = {Chen, Lin Y and Sotoodehnia, Nona and B{\r u}zkov{\'a}, Petra and Lopez, Faye L and Yee, Laura M and Heckbert, Susan R and Prineas, Ronald and Soliman, Elsayed Z and Adabag, Selcuk and Konety, Suma and Folsom, Aaron R and Siscovick, David and Alonso, Alvaro} } @article {6001, title = {Blood pressure variability and the risk of all-cause mortality, incident myocardial infarction, and incident stroke in the cardiovascular health study.}, journal = {Am J Hypertens}, volume = {26}, year = {2013}, month = {2013 Oct}, pages = {1210-7}, abstract = {

BACKGROUND: Recent reports have linked variability in visit-to-visit systolic blood pressure (SBP) to risk of mortality and stroke, independent of the effect of mean SBP level. This study aimed to evaluate whether variability in SBP is associated with all-cause mortality, incident myocardial infarction (MI), and incident stroke, independent of mean SBP or trends in SBP levels over time.

METHODS: The Cardiovascular Health Study is a longitudinal cohort study of vascular risk factors and disease in the elderly. Participants who attended their first 5 annual clinic visits and experienced no event before the 5th visit were eligible (n = 3,852). Primary analyses were restricted to participants not using antihypertensive medications throughout the first 5 clinic visits (n = 1,642). Intraindividual SBP variables were defined using each participant{\textquoteright}s 5-visit blood pressure measures. Cox proportional hazards models estimated adjusted hazard ratios (HRs) per SD increase in intraindividual SBP variability, adjusted for intraindividual SBP mean and change over time.

RESULTS: Over a mean follow-up of 9.9 years, there were 844 deaths, 203 MIs, and 195 strokes. Intraindividual SBP variability was significantly associated with increased risk of mortality (HR = 1.13; 95\% confidence interval (CI) = 1.05-1.21) and of incident MI (HR = 1.20; 95\%CI = 1.06-1.36), independent of the effect from adjustment factors. Intraindividual SBP variability was not associated with risk of stroke (HR = 1.03; 95\% CI = 0.89-1.21).

CONCLUSIONS: Long-term visit-to-visit SBP variability was independently associated with a higher risk of subsequent mortality and MI but not stroke. More research is needed to determine the relationship of BP variability with cardiovascular risk and the clinical implications.

}, keywords = {Aged, Blood Pressure, Cohort Studies, Female, Humans, Incidence, Longitudinal Studies, Male, Mortality, Myocardial Infarction, Risk, Stroke, United States}, issn = {1941-7225}, doi = {10.1093/ajh/hpt092}, author = {Suchy-Dicey, Astrid M and Wallace, Erin R and Mitchell, S V Elkind and Aguilar, Maria and Gottesman, Rebecca F and Rice, Kenneth and Kronmal, Richard and Psaty, Bruce M and Longstreth, W T} } @article {6030, title = {The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium as a model of collaborative science.}, journal = {Epidemiology}, volume = {24}, year = {2013}, month = {2013 May}, pages = {346-8}, keywords = {Aging, Cohort Studies, Cooperative Behavior, Genome-Wide Association Study, Heart Failure, Humans, Incidence, Multicenter Studies as Topic, Myocardial Infarction, Research Support as Topic, Stroke, United States}, issn = {1531-5487}, doi = {10.1097/EDE.0b013e31828b2cbb}, author = {Psaty, Bruce M and Sitlani, Colleen} } @article {6193, title = {Epidemiology and long-term clinical and biologic risk factors for pneumonia in community-dwelling older Americans: analysis of three cohorts.}, journal = {Chest}, volume = {144}, year = {2013}, month = {2013 Sep}, pages = {1008-1017}, abstract = {

BACKGROUND: Preventing pneumonia requires better understanding of incidence, mortality, and long-term clinical and biologic risk factors, particularly in younger individuals.

METHODS: This was a cohort study in three population-based cohorts of community-dwelling individuals. A derivation cohort (n = 16,260) was used to determine incidence and survival and develop a risk prediction model. The prediction model was validated in two cohorts (n = 8,495). The primary outcome was 10-year risk of pneumonia hospitalization.

RESULTS: The crude and age-adjusted incidences of pneumonia were 6.71 and 9.43 cases/1,000 person-years (10-year risk was 6.15\%). The 30-day and 1-year mortality were 16.5\% and 31.5\%. Although age was the most important risk factor (range of crude incidence rates, 1.69-39.13 cases/1,000 person-years for each 5-year increment from 45-85 years), 38\% of pneumonia cases occurred in adults \< 65 years of age. The 30-day and 1-year mortality were 12.5\% and 25.7\% in those \< 65 years of age. Although most comorbidities were associated with higher risk of pneumonia, reduced lung function was the most important risk factor (relative risk = 6.61 for severe reduction based on FEV1 by spirometry). A clinical risk prediction model based on age, smoking, and lung function predicted 10-year risk (area under curve [AUC] = 0.77 and Hosmer-Lemeshow [HL] C statistic = 0.12). Model discrimination and calibration were similar in the internal validation cohort (AUC = 0.77; HL C statistic, 0.65) but lower in the external validation cohort (AUC = 0.62; HL C statistic, 0.45). The model also calibrated well in blacks and younger adults. C-reactive protein and IL-6 were associated with higher pneumonia risk but did not improve model performance.

CONCLUSIONS: Pneumonia hospitalization is common and associated with high mortality, even in younger healthy adults. Long-term risk of pneumonia can be predicted in community-dwelling adults with a simple clinical risk prediction model.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Community-Acquired Infections, Comorbidity, Female, Follow-Up Studies, Hospitalization, Humans, Incidence, Male, Middle Aged, Pneumonia, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Survival Rate, Time Factors}, issn = {1931-3543}, doi = {10.1378/chest.12-2818}, author = {Yende, Sachin and Alvarez, Karina and Loehr, Laura and Folsom, Aaron R and Newman, Anne B and Weissfeld, Lisa A and Wunderink, Richard G and Kritchevsky, Stephen B and Mukamal, Kenneth J and London, Stephanie J and Harris, Tamara B and Bauer, Doug C and Angus, Derek C} } @article {5856, title = {Exploring psychosocial pathways between neighbourhood characteristics and stroke in older adults: the cardiovascular health study.}, journal = {Age Ageing}, volume = {42}, year = {2013}, month = {2013 May}, pages = {391-7}, abstract = {

OBJECTIVES: to investigate whether psychosocial pathways mediate the association between neighbourhood socioeconomic disadvantage and stroke.

METHODS: prospective cohort study with a follow-up of 11.5 years.

SETTING: the Cardiovascular Health Study, a longitudinal population-based cohort study of older adults >=65 years.

MEASUREMENTS: the primary outcome was adjudicated incident ischaemic stroke. Neighbourhood socioeconomic status (NSES) was measured using a composite of six census-tract variables. Psychosocial factors were assessed with standard measures for depression, social support and social networks.

RESULTS: of the 3,834 white participants with no prior stroke, 548 had an incident ischaemic stroke over the 11.5-year follow-up. Among whites, the incident stroke hazard ratio (HR) associated with living in the lowest relative to highest NSES quartile was 1.32 (95\% CI = 1.01-1.73), in models adjusted for individual SES. Additional adjustment for psychosocial factors had a minimal effect on hazard of incident stroke (HR = 1.31, CI = 1.00-1.71). Associations between NSES and stroke incidence were not found among African-Americans (n = 785) in either partially or fully adjusted models.

CONCLUSIONS: psychosocial factors played a minimal role in mediating the effect of NSES on stroke incidence among white older adults.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Aging, Brain Ischemia, Depression, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Linear Models, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Residence Characteristics, Risk Assessment, Risk Factors, Social Support, Socioeconomic Factors, Stroke, Time Factors, United States, Vulnerable Populations}, issn = {1468-2834}, doi = {10.1093/ageing/afs179}, author = {Yan, Tingjian and Escarce, Jos{\'e} J and Liang, Li-Jung and Longstreth, W T and Merkin, Sharon Stein and Ovbiagele, Bruce and Vassar, Stefanie D and Seeman, Teresa and Sarkisian, Catherine and Brown, Arleen F} } @article {1552, title = {Fetuin-A, type 2 diabetes, and risk of cardiovascular disease in older adults: the cardiovascular health study.}, journal = {Diabetes Care}, volume = {36}, year = {2013}, month = {2013 May}, pages = {1222-8}, abstract = {

OBJECTIVE: Fetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes.

RESEARCH DESIGN AND METHODS: This was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008.

RESULTS: Mean age was 75 years, and 61\% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95\% CI, 0.88-0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93-1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85-0.97) and 0.87 (0.79-0.95), respectively].

CONCLUSIONS: The association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Fetuins, Humans, Incidence, Longitudinal Studies, Male, Risk Factors}, issn = {1935-5548}, doi = {10.2337/dc12-1591}, author = {Jensen, Majken K and Bartz, Traci M and Mukamal, Kenneth J and Djouss{\'e}, Luc and Kizer, Jorge R and Tracy, Russell P and Zieman, Susan J and Rimm, Eric B and Siscovick, David S and Shlipak, Michael and Ix, Joachim H} } @article {1620, title = {Genetic analysis of a population heavy drinking phenotype identifies risk variants in whites.}, journal = {J Clin Psychopharmacol}, volume = {33}, year = {2013}, month = {2013 Apr}, pages = {206-10}, chapter = {206}, abstract = {

Genetic association studies thus far have used detailed diagnoses of alcoholism to identify loci associated with risk. This proof-of-concept analysis examined whether population data of lifetime heaviest alcohol consumption may be used to identify genetic loci that modulate risk. We conducted a genetic association study in European Americans between variants in approximately 2100 genes and alcohol consumption as part of the Candidate gene Association Resource project. We defined cases as individuals with a history of drinking 5 or more drinks per day almost every day of the week and controls as current light drinkers (1-5 drinks per week). We cross-validated identified single nucleotide polymorphisms in a meta-analysis of 2 cohorts of unrelated individuals--Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS)--and in a separate cohort of related individuals--Framingham Heart Study (FHS). The most significant variant in the meta-analysis of ARIC and CHS was rs6933598 in methylenetetrahydrofolate dehydrogenase (P = 7.46 {\texttimes} 10(-05)) with a P value in FHS of 0.042. The top variants in FHS were rs12249562 in cubulin (P = 3.03 {\texttimes} 10(-05)) and rs9839267 near cholecystokinin (P = 3.05 {\texttimes} 10(-05)) with a P value of 0.019 for rs9839267 in CHS. We have here shown feasibility in evaluating lifetime incidence of heavy alcohol drinking from population-based studies for the purpose of conducting genetic association analyses.

}, keywords = {Aged, Alcohol Drinking, Alcoholism, Case-Control Studies, European Continental Ancestry Group, Feasibility Studies, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Humans, Incidence, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk}, issn = {1533-712X}, doi = {10.1097/JCP.0b013e318287009a}, author = {Hamidovic, Ajna and Goodloe, Robert J and Young, Taylor R and Styn, Mindi A and Mukamal, Kenneth J and Choquet, Helene and Kasberger, Jay L and Buxbaum, Sarah G and Papanicolaou, George J and White, Wendy and Volcik, Kelly and Spring, Bonnie and Hitsman, Brian and Levy, Daniel and Jorgenson, Eric} } @article {1358, title = {Height and risk of incident intraparenchymal hemorrhage: Atherosclerosis Risk in Communities and Cardiovascular Health study cohorts.}, journal = {J Stroke Cerebrovasc Dis}, volume = {22}, year = {2013}, month = {2013 May}, pages = {323-8}, abstract = {

BACKGROUND: Height is inversely associated with incident coronary disease and total stroke, but few studies have examined the association between height and intraparenchymal hemorrhage (IPH). We hypothesized that height would be inversely associated with incident IPH in the combined cohorts of the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study.

METHODS: Data on Caucasian and African American participants were used to estimate the association of height at baseline with incident IPH verified by clinician review of medical records and imaging reports. Sex-specific Cox proportional hazards regression models were used to calculate hazard ratios.

RESULTS: A total of 20,983 participants initially free of stroke (11,788 women and 9195 men) were followed for an average of 15.9 years (standard deviation [SD] 5.1 years). Incident IPH occurred in 115 women and 73 men. Sex, but not age, race, study, or blood pressure, modified the association (P = .03). After adjustment for risk factors (age, systolic blood pressure, triglycerides, low-density lipoprotein cholesterol, fibrinogen, and race), among women, height was significantly inversely associated with incident IPH (hazard ratio [HR] per SD [6.3 cm] was 0.81; 95\% confidence interval [CI] 0.66-0.99; P = .04). The HR for tertile 3 vs 1 in women was 0.63 (95\% CI 0.37-1.08). Among men, height was not linearly associated with incident IPH (HR per SD [6.7 cm] was 1.09; 95\% CI 0.84-1.40; P = .52).

CONCLUSIONS: This large prospective study provides evidence that shorter height may be a risk factor for incident IPH in women.

}, keywords = {African Americans, Aged, Body Height, Cerebral Hemorrhage, European Continental Ancestry Group, Female, Humans, Incidence, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1532-8511}, doi = {10.1016/j.jstrokecerebrovasdis.2011.09.004}, author = {Smith, Lindsay G and Yatsuya, Hiroshi and Psaty, Bruce M and Longstreth, W T and Folsom, Aaron R} } @article {6167, title = {Impact of inflammatory biomarkers on relation of high density lipoprotein-cholesterol with incident coronary heart disease: cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {231}, year = {2013}, month = {2013 Dec}, pages = {246-51}, abstract = {

BACKGROUND: Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown.

OBJECTIVE: Investigate inflammatory markers{\textquoteright} individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD).

METHODS: In 3888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA$_{2}$) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA$_{2}$ values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA$_{2}$ was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events.

RESULTS: CHD incidence (per 1000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR = 1.50, p < 0.01) or highest IL-6 tertile (HR = 1.40, p < 0.05), but not with highest Lp-PLA$_{2}$ tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index.

CONCLUSION: The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, African Americans, Aged, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, HDL, Coronary Disease, European Continental Ancestry Group, Female, Humans, Incidence, Inflammation, Interleukin-6, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.08.036}, author = {Tehrani, David M and Gardin, Julius M and Yanez, David and Hirsch, Calvin H and Lloyd-Jones, Donald M and Stein, Phyllis K and Wong, Nathan D} } @article {5845, title = {Insulin resistance and risk of incident heart failure: Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {6}, year = {2013}, month = {2013 May}, pages = {364-70}, abstract = {

BACKGROUND: Patients with heart failure (HF) have higher fasting insulin levels and a higher prevalence of insulin resistance as compared with matched controls. Insulin resistance leads to structural abnormalities in the heart, such as increased left atrial size, left ventricular mass, and alterations in transmitral velocity that can precede the diagnosis of HF. It is not known whether insulin resistance precedes the development of HF or whether the relationship between insulin resistance and HF is present among adults with HF caused by nonischemic heart disease.

METHODS AND RESULTS: We examined 4425 participants (60\% women) from the Cardiovascular Health Study after excluding those with HF, myocardial infarction, or treated diabetes mellitus at baseline. We used Cox proportional hazards models to estimate the relative risk of incident HF associated with fasting insulin measured at study entry. There were 1216 cases of incident HF (1103 without antecedent myocardial infarction) during a median follow-up of 12 years (maximum, 19 years). Fasting insulin levels were positively associated with the risk of incident HF (hazard ratio, 1.10; 95\% confidence interval, 1.05-1.15, per SD change) when adjusted for age, sex, race, field center, physical activity, smoking, alcohol intake, high-density lipoprotein-cholesterol, total cholesterol, systolic blood pressure, and waist circumference. The association between fasting insulin levels and incident HF was similar for HF without antecedent myocardial infarction (hazard ratio, 1.10; 95\% confidence interval, 1.05-1.15). Measures of left atrial size, left ventricular mass, and peak A velocity at baseline were associated both with fasting insulin levels and with HF; however, additional statistical adjustment for these parameters did not completely attenuate the insulin-HF estimate (hazard ratio, 1.08; 95\% confidence interval, 1.03-1.14 per 1-SD increase in fasting insulin).

CONCLUSIONS: Fasting insulin was positively associated with adverse echocardiographic features and risk of subsequent HF in Cardiovascular Health Study participants, including those without an antecedent myocardial infarction.

CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

}, keywords = {Aged, Female, Heart Atria, Heart Failure, Heart Ventricles, Humans, Incidence, Insulin, Insulin Resistance, Male, Middle Aged, Myocardial Infarction, Organ Size, Proportional Hazards Models, Prospective Studies}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.112.000022}, author = {Banerjee, Dipanjan and Biggs, Mary L and Mercer, Laina and Mukamal, Kenneth and Kaplan, Robert and Barzilay, Joshua and Kuller, Lewis and Kizer, Jorge R and Djouss{\'e}, Luc and Tracy, Russell and Zieman, Susan and Lloyd-Jones, Donald and Siscovick, David and Carnethon, Mercedes} } @article {6136, title = {Kidney function and prevalent and incident frailty.}, journal = {Clin J Am Soc Nephrol}, volume = {8}, year = {2013}, month = {2013 Dec}, pages = {2091-9}, abstract = {

BACKGROUND AND OBJECTIVES: Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: CHS enrolled community-dwelling adults age >=65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.

RESULTS: The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24\% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) >=90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95\% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95\% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95\% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95\% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95\% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95\% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.

CONCLUSIONS: In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, Creatinine, Cross-Sectional Studies, Cystatin C, Fatigue, Female, Frail Elderly, Geriatric Assessment, Glomerular Filtration Rate, Humans, Incidence, Independent Living, Kidney, Kidney Diseases, Logistic Models, Male, Motor Activity, Multivariate Analysis, Muscle Weakness, Odds Ratio, Phenotype, Prevalence, Prospective Studies, Risk Factors, Time Factors, United States, Weight Loss}, issn = {1555-905X}, doi = {10.2215/CJN.02870313}, author = {Dalrymple, Lorien S and Katz, Ronit and Rifkin, Dena E and Siscovick, David and Newman, Anne B and Fried, Linda F and Sarnak, Mark J and Odden, Michelle C and Shlipak, Michael G} } @article {5848, title = {Long-chain monounsaturated Fatty acids and incidence of congestive heart failure in 2 prospective cohorts.}, journal = {Circulation}, volume = {127}, year = {2013}, month = {2013 Apr 09}, pages = {1512-21, 1521e1-18}, chapter = {1512}, abstract = {

BACKGROUND: Decades-old animal experiments suggested that dietary long-chain monounsaturated fatty acids (LCMUFAs) caused cardiotoxicity, leading, for example, development of Canola oil (Canadian oil low in erucic acid) from rapeseed. However, potential cardiotoxicity in humans and contemporary dietary sources of LCMUFAs are unknown.

METHODS AND RESULTS: We prospectively investigated the associations of plasma phospholipid LCMUFAs (20:1, 22:1, and 24:1), assessed as objective biomarkers of exposure, with incidence congestive heart failure in 2 independent cohorts: 3694 older adults (mean age, 75.2{\textpm}5.2 years) in the Cardiovascular Health Study (CHS; 1992-2006) and 3577 middle-aged adults (mean age, 54.1{\textpm}5.8 years) in the Atherosclerosis Risk in Communities Study, Minnesota subcohort (ARIC; 1987-2008). We further examined dietary correlates of circulating LCMUFAs in CHS and ARIC and US dietary sources of LCMUFAs in the 2003-2010 National Health and Nutrition Examination Survey (NHANES). In CHS, 997 congestive heart failure events occurred during 39 238 person-years; in ARIC, 330 events congestive heart failure events occurred during 64 438 person-years. After multivariable adjustment, higher levels of 22:1 and 24:1 were positively associated with greater incident congestive heart failure in both CHS and ARIC; hazard ratios were 1.34 (95\% confidence interval, 1.02-1.76) and 1.57 (95\% confidence interval, 1.11-2.23) for highest versus lowest quintiles of 22:1, respectively, and 1.75 (95\% confidence interval, 1.23-2.50) and 1.92 (95\% confidence interval, 1.22-3.03) for 24:1, respectively (P for trend <=0.03 each). A variety of foods were related to circulating LCMUFAs in CHS and ARIC, consistent with food sources of LCMUFAs in NHANES, including fish, poultry, meats, whole grains, and mustard.

CONCLUSIONS: Higher circulating levels of 22:1 and 24:1, with apparently diverse dietary sources, were associated with incident congestive heart failure in 2 independent cohorts, suggesting possible cardiotoxicity of LCMUFAs in humans.

}, keywords = {Aged, Aged, 80 and over, Cross-Sectional Studies, Dietary Fats, Fatty Acids, Monounsaturated, Feeding Behavior, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Nutrition Surveys, Prospective Studies, Risk Factors, Stroke}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.112.001197}, author = {Imamura, Fumiaki and Lemaitre, Rozenn N and King, Irena B and Song, Xiaoling and Steffen, Lyn M and Folsom, Aaron R and Siscovick, David S and Mozaffarian, Dariush} } @article {5855, title = {Neighborhood socioeconomic disadvantage and mortality after stroke.}, journal = {Neurology}, volume = {80}, year = {2013}, month = {2013 Feb 05}, pages = {520-7}, chapter = {520}, abstract = {

OBJECTIVE: Residence in a socioeconomically disadvantaged community is associated with mortality, but the mechanisms are not well understood. We examined whether socioeconomic features of the residential neighborhood contribute to poststroke mortality and whether neighborhood influences are mediated by traditional behavioral and biologic risk factors.

METHODS: We used data from the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults >=65 years. Residential neighborhood disadvantage was measured using neighborhood socioeconomic status (NSES), a composite of 6 census tract variables representing income, education, employment, and wealth. Multilevel Cox proportional hazard models were constructed to determine the association of NSES to mortality after an incident stroke, adjusted for sociodemographic characteristics, stroke type, and behavioral and biologic risk factors.

RESULTS: Among the 3,834 participants with no prior stroke at baseline, 806 had a stroke over a mean 11.5 years of follow-up, with 168 (20\%) deaths 30 days after stroke and 276 (34\%) deaths at 1 year. In models adjusted for demographic characteristics, stroke type, and behavioral and biologic risk factors, mortality hazard 1 year after stroke was significantly higher among residents of neighborhoods with the lowest NSES than those in the highest NSES neighborhoods (hazard ratio 1.77, 95\% confidence interval 1.17-2.68).

CONCLUSION: Living in a socioeconomically disadvantaged neighborhood is associated with higher mortality hazard at 1 year following an incident stroke. Further work is needed to understand the structural and social characteristics of neighborhoods that may contribute to mortality in the year after a stroke and the pathways through which these characteristics operate.

}, keywords = {Aged, Female, Humans, Incidence, Kaplan-Meier Estimate, Male, Proportional Hazards Models, Residence Characteristics, Risk Factors, Socioeconomic Factors, Stroke, Vulnerable Populations}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e31828154ae}, author = {Brown, Arleen F and Liang, Li-Jung and Vassar, Stefanie D and Merkin, Sharon Stein and Longstreth, W T and Ovbiagele, Bruce and Yan, Tingjian and Escarce, Jos{\'e} J} } @article {1551, title = {Persistent subclinical hypothyroidism and cardiovascular risk in the elderly: the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {98}, year = {2013}, month = {2013 Feb}, pages = {533-40}, abstract = {

CONTEXT: Use of a single set of thyroid function tests to define subclinical hypothyroidism may lead to misclassification over time and could influence findings from longitudinal studies.

OBJECTIVE: We assessed the risks of coronary heart disease (CHD), heart failure (HF), and cardiovascular (CV) death in older adults with persistent subclinical hypothyroidism.

DESIGN, SETTING, AND PARTICIPANTS: The study included 679 subclinically hypothyroid and 4184 euthyroid U.S. individuals at least 65 yr old enrolled in the Cardiovascular Health Study and not taking thyroid preparations.

MAIN OUTCOME MEASURE: We measured the 10-yr risk of incident CHD, HF, and CV death from persistent subclinical hypothyroidism, overall and stratified by degree of TSH elevation (4.5-6.9, 7.0-9.9, and 10.0-19.9 mU/liter).

RESULTS: There was no association between persistent subclinical hypothyroidism and incident CHD [hazard ratio (HR), 1.12; 95\% confidence interval (CI), 0.93-1.36], HF (HR, 1.05; 95\% CI, 0.97-1.27), or CV death (HR, 1.07; 95\% CI, 0.87-1.31) in adjusted analyses in which subclinical hypothyroidism was modeled as a time-varying exposure using up to four serial thyroid function tests. When subclinical hypothyroidism was stratified by degree of TSH elevation, no significant associations were found in any stratum. Findings were similar in fixed exposure analyses in which only participants with testing 2 yr apart were considered, with no association between persistent or transient subclinical hypothyroidism and incident CHD, HF, or CV death.

CONCLUSIONS: Our data do not support increased risk of CHD, HF, or CV death in older adults with persistent subclinical hypothyroidism.

}, keywords = {Aged, Aged, 80 and over, Coronary Disease, Female, Heart Failure, Humans, Hypothyroidism, Incidence, Longitudinal Studies, Male, Risk, Thyroid Function Tests}, issn = {1945-7197}, doi = {10.1210/jc.2012-2180}, author = {Hyland, Kristen A and Arnold, Alice M and Lee, Jennifer S and Cappola, Anne R} } @article {6064, title = {Plasma free fatty acids and risk of heart failure: the Cardiovascular Health Study.}, journal = {Circ Heart Fail}, volume = {6}, year = {2013}, month = {2013 Sep 01}, pages = {964-9}, abstract = {

BACKGROUND: Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes mellitus and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF).

METHODS AND RESULTS: To test the hypothesis that plasma concentration of FFAs is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and >65 years old from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per SD of FFAs. During a median follow-up of 10.5 years, a total of 1286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12\% (95\% confidence interval, 6\%-19\%) higher risk of HF. Controlling for time-varying diabetes mellitus and coronary heart disease did not change the results (hazard ratio per SD, 1.16 [95\% confidence interval, 1.09-1.23]).

CONCLUSIONS: A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biological mechanisms by which FFAs may influence the risk of HF and determine whether FFAs could serve as a novel pharmacological target for HF prevention.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Comorbidity, Fatty Acids, Nonesterified, Female, Heart Failure, Humans, Incidence, Kaplan-Meier Estimate, Linear Models, Male, Multivariate Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Time Factors, United States}, issn = {1941-3297}, doi = {10.1161/CIRCHEARTFAILURE.113.000521}, author = {Djouss{\'e}, Luc and Benkeser, David and Arnold, Alice and Kizer, Jorge R and Zieman, Susan J and Lemaitre, Rozenn N and Tracy, Russell P and Gottdiener, John S and Mozaffarian, Dariush and Siscovick, David S and Mukamal, Kenneth J and Ix, Joachim H} } @article {5998, title = {The QT interval and risk of incident atrial fibrillation.}, journal = {Heart Rhythm}, volume = {10}, year = {2013}, month = {2013 Oct}, pages = {1562-8}, abstract = {

BACKGROUND: Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine.

OBJECTIVE: To determine whether the QT interval, a marker of ventricular repolarization, could be used to predict incident AF.

METHODS: We examined a prolonged QT interval corrected by using the Framingham formula (QT(Fram)) as a predictor of incident AF in the Atherosclerosis Risk in Communities (ARIC) study. The Cardiovascular Health Study (CHS) and Health, Aging, and Body Composition (ABC) study were used for validation. Secondary predictors included QT duration as a continuous variable, a short QT interval, and QT intervals corrected by using other formulas.

RESULTS: Among 14,538 ARIC study participants, a prolonged QT(Fram) predicted a roughly 2-fold increased risk of AF (hazard ratio [HR] 2.05; 95\% confidence interval [CI] 1.42-2.96; P < .001). No substantive attenuation was observed after adjustment for age, race, sex, study center, body mass index, hypertension, diabetes, coronary disease, and heart failure. The findings were validated in Cardiovascular Health Study and Health, Aging, and Body Composition study and were similar across various QT correction methods. Also in the ARIC study, each 10-ms increase in QT(Fram) was associated with an increased unadjusted (HR 1.14; 95\% CI 1.10-1.17; P < .001) and adjusted (HR 1.11; 95\% CI 1.07-1.14; P < .001) risk of AF. Findings regarding a short QT interval were inconsistent across cohorts.

CONCLUSIONS: A prolonged QT interval is associated with an increased risk of incident AF.

}, keywords = {Aged, Atrial Fibrillation, Cohort Studies, Electrocardiography, Female, Humans, Incidence, Long QT Syndrome, Male, Middle Aged, Risk Factors}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2013.07.023}, author = {Mandyam, Mala C and Soliman, Elsayed Z and Alonso, Alvaro and Dewland, Thomas A and Heckbert, Susan R and Vittinghoff, Eric and Cummings, Steven R and Ellinor, Patrick T and Chaitman, Bernard R and Stocke, Karen and Applegate, William B and Arking, Dan E and Butler, Javed and Loehr, Laura R and Magnani, Jared W and Murphy, Rachel A and Satterfield, Suzanne and Newman, Anne B and Marcus, Gregory M} } @article {5852, title = {Racial differences in the incidence of and risk factors for atrial fibrillation in older adults: the cardiovascular health study.}, journal = {J Am Geriatr Soc}, volume = {61}, year = {2013}, month = {2013 Feb}, pages = {276-80}, abstract = {

This study examined whether different associations between risk factors and atrial fibrillation (AF) according to race could explain the lower incidence of AF in blacks. Baseline risk factor information was obtained from interviews, clinical examinations, and echocardiography in 4,774 white and 911 black Cardiovascular Health Study participants aged 65 and older without a history of AF at baseline in 1989/90 or 1992/93. Incident AF was determined according to hospital discharge diagnosis or annual study electrocardiogram. Cox regression was used to assess associations between risk factors and race and incident AF. During a mean 11.2 years of follow-up, 1,403 whites and 182 blacks had incident AF. Associations between all examined risk factors were similar in both races, except left ventricular posterior wall thickness, which was more strongly associated with AF in blacks (per 0.2 cm, blacks: hazard ratio (HR) = 1.72, 95\% confidence interval (CI) = 1.44-2.06; whites: HR = 1.30, 95\% CI = 1.18-1.43). Overall, the relative risk of AF was 25\% lower in blacks than whites after adjustment for age and sex (HR = 0.75, 95\% CI = 0.64-0.87) and 45\% lower after adjustment for all considered risk factors (HR = 0.55, 95\% CI = 0.35-0.88). Different associations of the considered risk factors and incident AF by race do not explain the lower incidence of AF in blacks.

}, keywords = {Aged, Atrial Fibrillation, Continental Population Groups, Female, Follow-Up Studies, Humans, Incidence, Male, Prevalence, Risk Assessment, Risk Factors, Stroke, United States}, issn = {1532-5415}, doi = {10.1111/jgs.12085}, author = {Jensen, Paul N and Thacker, Evan L and Dublin, Sascha and Psaty, Bruce M and Heckbert, Susan R} } @article {1559, title = {Relation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {111}, year = {2013}, month = {2013 Feb 01}, pages = {418-24}, abstract = {

Vitamin D and parathyroid hormone (PTH) may affect cardiovascular health in patients with kidney disease and in the general population. The aim of this study was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic, and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH concentrations were measured using mass spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9 {\textpm} 4.9 years, 69.7\% were women, and 21\% had chronic kidney disease (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 {\textpm} 10.2 ng/ml, and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels >=65 pg/ml were associated with greater N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in patients with chronic kidney disease. The regression coefficients were: 120 pg/ml (95\% confidence interval 36.1 to 204), 5.2 pg/ml (95\% confidence interval 3.0 to 7.4), and 17 g (95\% confidence interval 6.2 to 27.8) (p <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. In conclusion, in older adults with chronic kidney disease, PTH excess is associated with higher N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass. These findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases.

}, keywords = {Adult, Aged, Biomarkers, Cardiovascular Diseases, Echocardiography, Electrocardiography, Female, Follow-Up Studies, Heart Ventricles, Humans, Incidence, Male, Mass Spectrometry, Middle Aged, Parathyroid Hormone, Prospective Studies, United States, Vitamin D}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2012.10.021}, author = {van Ballegooijen, Adriana J and Visser, Marjolein and Kestenbaum, Bryan and Siscovick, David S and de Boer, Ian H and Gottdiener, John S and deFilippi, Christopher R and Brouwer, Ingeborg A} } @article {5994, title = {Risk factors for type 2 diabetes mellitus preceded by β-cell dysfunction, insulin resistance, or both in older adults: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {177}, year = {2013}, month = {2013 Jun 15}, pages = {1418-29}, chapter = {1418}, abstract = {

Insulin resistance (IR) and pancreatic β-cell dysfunction lead to type 2 diabetes mellitus (DM). We tested whether risk factors would differ for DM that was preceded predominantly by IR, β-cell dysfunction, or both among 4,384 older adults (mean age, 72.7 (standard deviation, 5.6) years) in the Cardiovascular Health Study, which was conducted in North Carolina, California, Maryland, and Pennsylvania (1989-2007). When evaluating established risk factors, we found older age, greater adiposity, higher systolic blood pressure, a lower high-density lipoprotein cholesterol level, a higher triglyceride level, and a lower alcohol intake to be independently associated with greater IR but, conversely, with better β-cell function (P < 0.001). The prospective associations between some risk factors and incident DM varied significantly depending on whether DM was preceded predominantly by IR, β-cell dysfunction, or both. For example, obesity and lower high-density lipoprotein cholesterol levels were positively associated with DM preceded predominantly by IR (hazard ratio (HR) = 5.02, 95\% confidence interval (CI): 2.81, 9.00; and HR = 1.97, 95\% CI: 1.32, 2.93, respectively), with a significant association with and an insignificant trend toward a lower risk of DM preceded predominantly by β-cell dysfunction (HR = 0.33, 95\% CI: 0.14, 0.80; and HR = 0.78, 95\% CI: 0.43, 1.39, respectively). In conclusion, among older adults, DM risk factors were differentially associated with DM preceded predominantly by IR or β-cell dysfunction. Biologic and clinical implications of putative subtypes of DM require further investigation.

}, keywords = {Adiposity, Age Factors, Aged, Aged, 80 and over, Aging, Alcohol Drinking, Blood Pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Incidence, Insulin Resistance, Insulin-Secreting Cells, Lipids, Male, Prospective Studies, Risk Factors, Socioeconomic Factors, United States}, issn = {1476-6256}, doi = {10.1093/aje/kws440}, author = {Imamura, Fumiaki and Mukamal, Kenneth J and Meigs, James B and Luchsinger, Jos{\'e} A and Ix, Joachim H and Siscovick, David S and Mozaffarian, Dariush} } @article {5878, title = {Simple risk model predicts incidence of atrial fibrillation in a racially and geographically diverse population: the CHARGE-AF consortium.}, journal = {J Am Heart Assoc}, volume = {2}, year = {2013}, month = {2013 Mar 18}, pages = {e000102}, abstract = {

BACKGROUND: Tools for the prediction of atrial fibrillation (AF) may identify high-risk individuals more likely to benefit from preventive interventions and serve as a benchmark to test novel putative risk factors.

METHODS AND RESULTS: Individual-level data from 3 large cohorts in the United States (Atherosclerosis Risk in Communities [ARIC] study, the Cardiovascular Health Study [CHS], and the Framingham Heart Study [FHS]), including 18 556 men and women aged 46 to 94 years (19\% African Americans, 81\% whites) were pooled to derive predictive models for AF using clinical variables. Validation of the derived models was performed in 7672 participants from the Age, Gene and Environment-Reykjavik study (AGES) and the Rotterdam Study (RS). The analysis included 1186 incident AF cases in the derivation cohorts and 585 in the validation cohorts. A simple 5-year predictive model including the variables age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure had good discrimination (C-statistic, 0.765; 95\% CI, 0.748 to 0.781). Addition of variables from the electrocardiogram did not improve the overall model discrimination (C-statistic, 0.767; 95\% CI, 0.750 to 0.783; categorical net reclassification improvement, -0.0032; 95\% CI, -0.0178 to 0.0113). In the validation cohorts, discrimination was acceptable (AGES C-statistic, 0.664; 95\% CI, 0.632 to 0.697 and RS C-statistic, 0.705; 95\% CI, 0.664 to 0.747) and calibration was adequate.

CONCLUSION: A risk model including variables readily available in primary care settings adequately predicted AF in diverse populations from the United States and Europe.

}, keywords = {African Americans, Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Cohort Studies, Diabetes Mellitus, European Continental Ancestry Group, Female, Heart Failure, Humans, Hypertension, Iceland, Incidence, Male, Middle Aged, Myocardial Infarction, Netherlands, Proportional Hazards Models, Risk Assessment, Smoking, United States}, issn = {2047-9980}, doi = {10.1161/JAHA.112.000102}, author = {Alonso, Alvaro and Krijthe, Bouwe P and Aspelund, Thor and Stepas, Katherine A and Pencina, Michael J and Moser, Carlee B and Sinner, Moritz F and Sotoodehnia, Nona and Fontes, Jo{\~a}o D and Janssens, A Cecile J W and Kronmal, Richard A and Magnani, Jared W and Witteman, Jacqueline C and Chamberlain, Alanna M and Lubitz, Steven A and Schnabel, Renate B and Agarwal, Sunil K and McManus, David D and Ellinor, Patrick T and Larson, Martin G and Burke, Gregory L and Launer, Lenore J and Hofman, Albert and Levy, Daniel and Gottdiener, John S and K{\"a}{\"a}b, Stefan and Couper, David and Harris, Tamara B and Soliman, Elsayed Z and Stricker, Bruno H C and Gudnason, Vilmundur and Heckbert, Susan R and Benjamin, Emelia J} } @article {1564, title = {Soluble CD14: genomewide association analysis and relationship to cardiovascular risk and mortality in older adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {33}, year = {2013}, month = {2013 Jan}, pages = {158-64}, abstract = {

OBJECTIVE: CD14 is a glycosylphosphotidylinositol-anchored membrane glycoprotein expressed on neutrophils and monocytes/macrophages that also circulates as a soluble form (sCD14). Despite the well-recognized role of CD14 in inflammation, relatively little is known about the genetic determinants of sCD14 or the relationship of sCD14 to vascular- and aging-related phenotypes.

METHODS AND RESULTS: We measured baseline levels of sCD14 in >5000 European-American and black adults aged 65 years and older from the Cardiovascular Health Study, who were well characterized at baseline for atherosclerotic risk factors and subclinical cardiovascular disease, and who have been followed for clinical cardiovascular disease and mortality outcomes up to 20 years. At baseline, sCD14 generally showed strong positive correlations with traditional cardio-metabolic risk factors and with subclinical measures of vascular disease such as carotid wall thickness and ankle-brachial index (independently of traditional cardiovascular disease risk factors), and was also inversely correlated with body mass index. In genomewide association analyses of sCD14, we (1) confirmed the importance of the CD14 locus on chromosome 5q21 in European-American; (2) identified a novel African ancestry-specific allele of CD14 associated with lower sCD14 in blacks; and (3) identified a putative novel association in European-American of a nonsynonymous variant of PIGC, which encodes an enzyme required for the first step in glycosylphosphotidylinositol anchor biosynthesis. Finally, we show that, like other acute phase inflammatory biomarkers, sCD14 predicts incident cardiovascular disease, and strongly and independently predicts all-cause mortality in older adults.

CONCLUSIONS: CD14 independently predicts risk mortality in older adults.

}, keywords = {African Americans, Age Factors, Aged, Biomarkers, Cardiovascular Diseases, Chromosomes, Human, Pair 5, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, Hexosyltransferases, Humans, Incidence, Inflammation Mediators, Linear Models, Lipopolysaccharide Receptors, Logistic Models, Male, Membrane Proteins, Multivariate Analysis, Phenotype, Polymorphism, Single Nucleotide, Principal Component Analysis, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.112.300421}, author = {Reiner, Alex P and Lange, Ethan M and Jenny, Nancy S and Chaves, Paulo H M and Ellis, Jaclyn and Li, Jin and Walston, Jeremy and Lange, Leslie A and Cushman, Mary and Tracy, Russell P} } @article {6576, title = {Advanced glycation/glycoxidation endproduct carboxymethyl-lysine and incidence of coronary heart disease and stroke in older adults.}, journal = {Atherosclerosis}, volume = {235}, year = {2014}, month = {2014 Jul}, pages = {116-21}, abstract = {

BACKGROUND: Advanced glycation/glycoxidation endproducts (AGEs) accumulate in settings of increased oxidative stress--such as diabetes, chronic kidney disease and aging--where they promote vascular stiffness and atherogenesis, but the prospective association between AGEs and cardiovascular events in elders has not been previously examined.

METHODS: To test the hypothesis that circulating levels of N(ɛ)-carboxymethyl-lysine (CML), a major AGE, increase the risk of incident coronary heart disease and stroke in older adults, we measured serum CML by immunoassay in 2111 individuals free of prevalent cardiovascular disease participating in a population-based study of U.S. adults ages 65 and older.

RESULTS: During median follow-up of 9.1 years, 625 cardiovascular events occurred. CML was positively associated with incident cardiovascular events after adjustment for age, sex, race, systolic blood pressure, anti-hypertensive treatment, diabetes, smoking status, triglycerides, albumin, and self-reported health status (hazard ratio [HR] per SD [0.99 pmol/l] increase=1.11, 95\% confidence interval [CI]=1.03-1.19). This association was not materially attenuated by additional adjustment for C-reactive protein, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio. Findings were similar for the component endpoints of coronary heart disease and stroke.

CONCLUSIONS: In this large older cohort, CML was associated with an increased risk of cardiovascular events independent of a wide array of potential confounders and mediators. Although the moderate association limits CML{\textquoteright}s value for risk prediction, these community-based findings provide support for clinical trials to test AGE-lowering therapies for cardiovascular prevention in this population.

}, keywords = {Aged, Albumins, Antihypertensive Agents, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Creatinine, Female, Glomerular Filtration Rate, Glycation End Products, Advanced, Humans, Immunoassay, Incidence, Lysine, Male, Oxidative Stress, Proportional Hazards Models, Stroke, Treatment Outcome}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2014.04.013}, author = {Kizer, Jorge R and Benkeser, David and Arnold, Alice M and Ix, Joachim H and Mukamal, Kenneth J and Djouss{\'e}, Luc and Tracy, Russell P and Siscovick, David S and Psaty, Bruce M and Zieman, Susan J} } @article {6543, title = {Association of sick sinus syndrome with incident cardiovascular disease and mortality: the Atherosclerosis Risk in Communities study and Cardiovascular Health Study.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e109662}, abstract = {

BACKGROUND: Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

METHODS: We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

RESULTS: During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95\% confidence interval [CI] 1.14-1.70), coronary heart disease (HR 1.72, 95\%CI 1.11-2.66), heart failure (HR 2.87, 95\%CI 2.17-3.80), stroke (HR 1.56, 95\%CI 0.99-2.46), AF (HR 5.75, 95\%CI 4.43-7.46), and pacemaker implantation (HR 53.7, 95\%CI 42.9-67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95\%CI 1.51-2.66), AF (HR 4.25, 95\%CI 3.28-5.51), and pacemaker implantation (HR 25.2, 95\%CI 19.8-32.1).

CONCLUSION: Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.

}, keywords = {Age Distribution, Atherosclerosis, Cohort Studies, Continental Population Groups, Female, Humans, Incidence, Male, Middle Aged, Residence Characteristics, Risk, Sex Distribution, Sick Sinus Syndrome}, issn = {1932-6203}, doi = {10.1371/journal.pone.0109662}, author = {Alonso, Alvaro and Jensen, Paul N and Lopez, Faye L and Chen, Lin Y and Psaty, Bruce M and Folsom, Aaron R and Heckbert, Susan R} } @article {6601, title = {B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies.}, journal = {Europace}, volume = {16}, year = {2014}, month = {2014 Oct}, pages = {1426-33}, abstract = {

AIMS: B-type natriuretic peptide (BNP) and C-reactive protein (CRP) predict atrial fibrillation (AF) risk. However, their risk stratification abilities in the broad community remain uncertain. We sought to improve risk stratification for AF using biomarker information.

METHODS AND RESULTS: We ascertained AF incidence in 18 556 Whites and African Americans from the Atherosclerosis Risk in Communities Study (ARIC, n=10 675), Cardiovascular Health Study (CHS, n = 5043), and Framingham Heart Study (FHS, n = 2838), followed for 5 years (prediction horizon). We added BNP (ARIC/CHS: N-terminal pro-B-type natriuretic peptide; FHS: BNP), CRP, or both to a previously reported AF risk score, and assessed model calibration and predictive ability [C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI)]. We replicated models in two independent European cohorts: Age, Gene/Environment Susceptibility Reykjavik Study (AGES), n = 4467; Rotterdam Study (RS), n = 3203. B-type natriuretic peptide and CRP were significantly associated with AF incidence (n = 1186): hazard ratio per 1-SD ln-transformed biomarker 1.66 [95\% confidence interval (CI), 1.56-1.76], P < 0.0001 and 1.18 (95\% CI, 1.11-1.25), P < 0.0001, respectively. Model calibration was sufficient (BNP, χ(2) = 17.0; CRP, χ(2) = 10.5; BNP and CRP, χ(2) = 13.1). B-type natriuretic peptide improved the C-statistic from 0.765 to 0.790, yielded an IDI of 0.027 (95\% CI, 0.022-0.032), a relative IDI of 41.5\%, and a continuous NRI of 0.389 (95\% CI, 0.322-0.455). The predictive ability of CRP was limited (C-statistic increment 0.003). B-type natriuretic peptide consistently improved prediction in AGES and RS.

CONCLUSION: B-type natriuretic peptide, not CRP, substantially improved AF risk prediction beyond clinical factors in an independently replicated, heterogeneous population. B-type natriuretic peptide may serve as a benchmark to evaluate novel putative AF risk biomarkers.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, C-Reactive Protein, Europe, Female, Humans, Incidence, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Risk Assessment, Risk Factors, United States}, issn = {1532-2092}, doi = {10.1093/europace/euu175}, author = {Sinner, Moritz F and Stepas, Katherine A and Moser, Carlee B and Krijthe, Bouwe P and Aspelund, Thor and Sotoodehnia, Nona and Fontes, Jo{\~a}o D and Janssens, A Cecile J W and Kronmal, Richard A and Magnani, Jared W and Witteman, Jacqueline C and Chamberlain, Alanna M and Lubitz, Steven A and Schnabel, Renate B and Vasan, Ramachandran S and Wang, Thomas J and Agarwal, Sunil K and McManus, David D and Franco, Oscar H and Yin, Xiaoyan and Larson, Martin G and Burke, Gregory L and Launer, Lenore J and Hofman, Albert and Levy, Daniel and Gottdiener, John S and K{\"a}{\"a}b, Stefan and Couper, David and Harris, Tamara B and Astor, Brad C and Ballantyne, Christie M and Hoogeveen, Ron C and Arai, Andrew E and Soliman, Elsayed Z and Ellinor, Patrick T and Stricker, Bruno H C and Gudnason, Vilmundur and Heckbert, Susan R and Pencina, Michael J and Benjamin, Emelia J and Alonso, Alvaro} } @article {6337, title = {Circulating fibrosis biomarkers and risk of atrial fibrillation: The Cardiovascular Health Study (CHS).}, journal = {Am Heart J}, volume = {167}, year = {2014}, month = {2014 May}, pages = {723-8.e2}, abstract = {

BACKGROUND: Cardiac fibrosis is thought to play a central role in the pathogenesis of atrial fibrillation (AF). Retrospective studies have suggested that circulating fibrosis biomarkers are associated with AF, but prospective studies are limited.

METHODS: We measured circulating levels of 2 fibrosis biomarkers, procollagen type III, N-terminal propeptide (PIIINP) and transforming growth factor β1 among participants of the CHS, a population-based study of older Americans. We used Cox proportional hazards and competing risks models to examine adjusted risk of incident AF over a median follow-up of 8.8 years.

RESULTS: Levels of PIIINP were assessed in 2,935 participants, of whom 767 developed AF. Compared with the median PIIINP level (4.45 μg/L), adjusted hazard ratios (95\% CIs) were 0.85 (0.72-1.00) at the 10th percentile, 0.93 (0.88-0.99) at the 25th percentile, 1.04 (0.95-1.04) at the 75th percentile, and 1.07 (0.90-1.26) at the 90th. Transforming growth factor β1 levels, assessed in 1,538 participants with 408 cases of incident AF, were not associated with AF risk.

CONCLUSION: In older adults, PIIINP levels were associated with risk of incident AF in a complex manner, with an association that appeared to be positive up to median levels but with little relationship beyond that. Further studies are required to confirm and possibly delineate the mechanism for this relationship.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, Cardiomyopathies, Electrocardiography, Enzyme-Linked Immunosorbent Assay, Female, Fibrosis, Follow-Up Studies, Humans, Incidence, Male, Peptide Fragments, Procollagen, Prospective Studies, Risk Factors, Time Factors, Transforming Growth Factor beta1, United States}, issn = {1097-6744}, doi = {10.1016/j.ahj.2014.01.010}, author = {Rosenberg, Michael A and Maziarz, Marlena and Tan, Alex Y and Glazer, Nicole L and Zieman, Susan J and Kizer, Jorge R and Ix, Joachim H and Djouss{\'e}, Luc and Siscovick, David S and Heckbert, Susan R and Mukamal, Kenneth J} } @article {6375, title = {Circulating levels of carboxy-methyl-lysine (CML) are associated with hip fracture risk: the Cardiovascular Health Study.}, journal = {J Bone Miner Res}, volume = {29}, year = {2014}, month = {2014}, pages = {1061-6}, abstract = {

Advanced glycation end products (AGE) in bone tissue are associated with impaired biomechanical properties and increased fracture risk. Here we examine whether serum levels of the AGE carboxy-methyl-lysine (CML) are associated with risk of hip fracture.We followed 3373 participants from the Cardiovascular Health Study (age 78 years; range, 68{\textendash}102 years; 39.8\% male) for a median of 9.22 years (range, 0.01{\textendash}12.07 years). Rates of incident hip fracture were calculated by quartiles of baseline CML levels, and hazard ratios were adjusted for covariates associated with hip fracture risk. A subcohort of 1315 participants had bone mineral density (BMD)measurement. There were 348 hip fractures during follow-up, with incidence rates of hip fracture by CML quartiles of 0.94, 1.34, 1.18, and 1.69 per 100 participant-years. The unadjusted hazard ratio of hip fracture increased with each 1 SD increase (189 ng/mL) of CML level (hazard ratio, 1.27; 95\% confidence interval [CI], 1.16{\textendash}1.40]; p<0.001). Sequential adjustment for age, gender, race/ethnicity,body mass index (BMI), smoking, alcohol consumption, prevalent coronary heart disease (CHD), energy expenditure, and estimated glomerular filtration rate (based on cystatin C), moderately attenuated the hazard ratio for fracture (1.17; 95\% CI, 1.05{\textendash}1.31; p=0.006).In the cohort with BMD testing, total hip BMD was not significantly associated with CML levels. We conclude that increasing levels of CML are associated with hip fracture risk in older adults, independent of hip BMD. These results implicate AGE in the pathogenesis of hip fractures.

}, keywords = {Age Factors, Aged, Female, Follow-Up Studies, Glycation End Products, Advanced, Hip Fractures, Humans, Incidence, Lysine, Male, Prospective Studies, Retrospective Studies, Risk Factors}, issn = {1523-4681}, author = {Barzilay, Joshua I and B{\r u}zkov{\'a}, Petra and Zieman, Susan J and Kizer, Jorge R and Djouss{\'e}, Luc and Ix, Joachim H and Tracy, Russell P and Siscovick, David S and Cauley, Jane A and Mukamal, Kenneth J} } @article {6188, title = {Enhancing case ascertainment of Parkinson{\textquoteright}s disease using Medicare claims data in a population-based cohort: the Cardiovascular Health Study.}, journal = {Pharmacoepidemiol Drug Saf}, volume = {23}, year = {2014}, month = {2014 Feb}, pages = {119-27}, abstract = {

PURPOSE: We sought to improve a previous algorithm to ascertain Parkinson{\textquoteright}s disease (PD) in the Cardiovascular Health Study by incorporating additional data from Medicare outpatient claims. We compared our results to the previous algorithm in terms of baseline prevalence and incidence of PD, as well as associations with baseline smoking characteristics.

METHODS: Our original case ascertainment used self-reported diagnosis, antiparkinsonian medication, and hospitalization discharge International Classification of Diseases-Ninth version code. In this study, we incorporated additional data from fee-for-service Medicare claims, extended follow-up time, review of hospitalization records, and adjudicated cause of death. Two movement disorders specialists adjudicated final PD status. We used logistic regression models and controlled for age, sex, African American race, and education.

RESULTS: We identified 75 additional cases but reclassified 80 previously identified cases as not having PD. We observed significant inverse association with smoking status (odds ratio = 0.42; 95\% confidence interval (CI) = 0.22, 0.79), and inverse linear trends with pack-years (p = 0.005), and cigarettes per day (p = 0.019) with incident PD. All estimates were stronger than those from the previous algorithm.

CONCLUSIONS: Our enhanced method did not alter prevalence and incidence estimates compared with our previous algorithm. However, our enhanced method provided stronger estimates of association, potentially due to reduced level of disease misclassification.

}, keywords = {Aged, Aged, 80 and over, Algorithms, Antiparkinson Agents, Cohort Studies, Databases, Factual, Female, Hospitalization, Humans, Incidence, Logistic Models, Male, Medicare, Parkinson Disease, Prevalence, Prospective Studies, Smoking, Time Factors, United States}, issn = {1099-1557}, doi = {10.1002/pds.3552}, author = {Ton, Thanh G N and Biggs, Mary Lou and Comer, Diane and Curtis, Lesley and Hu, Shu-Ching and Thacker, Evan L and Searles Nielsen, Susan and Delaney, Joseph A and Landsittel, Douglas and Longstreth, William T and Checkoway, Harvey and Jain, Samay} } @article {6239, title = {Fibroblast growth factor 23, the ankle-brachial index, and incident peripheral artery disease in the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {233}, year = {2014}, month = {2014 Mar}, pages = {91-6}, abstract = {

BACKGROUND: Fibroblast growth factor 23 (FGF23) has emerged as a novel risk factor for mortality and cardiovascular events. Its association with the ankle-brachial index (ABI) and clinical peripheral artery disease (PAD) is less known.

METHODS: Using data (N = 3143) from the Cardiovascular Health Study (CHS), a cohort of community dwelling adults >65 years of age, we analyzed the cross-sectional association of FGF23 with ABI and its association with incident clinical PAD events during 9.8 years of follow up using multinomial logistic regression and Cox proportional hazards models respectively.

RESULTS: The prevalence of cardiovascular disease (CVD) and traditional risk factors like diabetes, coronary artery disease, and heart failure increased across higher quartiles of FGF23. Compared to those with ABI of 1.1-1.4, FGF23 per doubling at baseline was associated with prevalent PAD (ABI < 0.9) although this association was attenuated after adjusting for CVD risk factors, and kidney function (OR 0.91, 95\% CI 0.76-1.08). FGF23 was not associated with high ABI (>1.4) (OR 1.06, 95\% CI 0.75-1.51). Higher FGF23 was associated with incidence of PAD events in unadjusted, demographic adjusted, and CVD risk factor adjusted models (HR 2.26, 95\% CI 1.28-3.98; highest versus lowest quartile). The addition of estimated glomerular filtration and urine albumin to creatinine ratio to the model however, attenuated these findings (HR 1.46, 95\% CI, 0.79-2.70).

CONCLUSIONS: In community dwelling older adults, FGF23 was not associated with baseline low or high ABI or incident PAD events after adjusting for confounding variables. These results suggest that FGF23 may primarily be associated with adverse cardiovascular outcomes through non atherosclerotic mechanisms.

}, keywords = {Aged, Ankle Brachial Index, Cardiovascular Diseases, Cross-Sectional Studies, Fibroblast Growth Factors, Humans, Incidence, Peripheral Arterial Disease, Risk Factors}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2013.12.015}, author = {Garimella, Pranav S and Ix, Joachim H and Katz, Ronit and Chonchol, Michel B and Kestenbaum, Bryan R and de Boer, Ian H and Siscovick, David S and Shastri, Shani and Hiramoto, Jade S and Shlipak, Michael G and Sarnak, Mark J} } @article {6541, title = {Fibrosis-related biomarkers and incident cardiovascular disease in older adults: the cardiovascular health study.}, journal = {Circ Arrhythm Electrophysiol}, volume = {7}, year = {2014}, month = {2014 Aug}, pages = {583-9}, abstract = {

BACKGROUND: Fibrotic changes in the heart and arteries have been implicated in a diverse range of cardiovascular diseases (CVD), but whether circulating biomarkers that reflect fibrosis are associated with CVD is unknown.

METHODS AND RESULTS: We determined the associations of 2 biomarkers of fibrosis, transforming growth factor- β (TGF-β), and procollagen type III N-terminal propeptide (PIIINP), with incident heart failure, myocardial infarction, and stroke among community-living older adults in the Cardiovascular Health Study. We measured circulating TGF-β (n=1371) and PIIINP (n=2568) from plasma samples collected in 1996 and ascertained events through 2010. Given TGF-β{\textquoteright}s pleiotropic effects on inflammation and fibrogenesis, we investigated potential effect modification by C-reactive protein in secondary analyses. After adjustment for sociodemographic, clinical, and biochemical risk factors, PIIINP was associated with total CVD (hazard ratio [HR] per SD=1.07; 95\% confidence interval [CI], 1.01-1.14) and heart failure (HR per SD=1.08; CI, 1.01-1.16) but not myocardial infarction or stroke. TGF-β was not associated with any CVD outcomes in the full cohort but was associated with total CVD (HR per SD=1.16; CI, 1.02-1.31), heart failure (HR per SD=1.16; CI, 1.01-1.34), and stroke (HR per SD=1.20; CI, 1.01-1.42) among individuals with C-reactive protein above the median, 2.3 mg/L (P interaction <0.05).

CONCLUSIONS: Our findings provide large-scale, prospective evidence that circulating biomarkers of fibrosis, measured in community-living individuals late in life, are associated with CVD. Further research on whether TGF-β has a stronger fibrogenic effect in the setting of inflammation is warranted.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Aging, Biomarkers, C-Reactive Protein, Cardiovascular Diseases, Female, Fibrosis, Heart Failure, Humans, Incidence, Male, Myocardial Infarction, Peptide Fragments, Procollagen, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Stroke, Time Factors, Transforming Growth Factor beta, United States}, issn = {1941-3084}, doi = {10.1161/CIRCEP.114.001610}, author = {Agarwal, Isha and Glazer, Nicole L and Barasch, Eddy and Biggs, Mary L and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Gottdiener, John S and Ix, Joachim H and Kizer, Jorge R and Rimm, Eric B and Sicovick, David S and Tracy, Russell P and Mukamal, Kenneth J} } @article {6187, title = {Height and risk of sudden cardiac death: the Atherosclerosis Risk in Communities and Cardiovascular Health studies.}, journal = {Ann Epidemiol}, volume = {24}, year = {2014}, month = {2014 Mar}, pages = {174-179.e2}, abstract = {

PURPOSE: Sudden cardiac death (SCD) is an important cause of mortality in the adult population. Height has been associated with cardiac hypertrophy and an increased risk of arrhythmias but also with decreased risk of coronary heart disease, suggesting a complex association with SCD.

METHODS: We examined the association of adult height with the risk of physician-adjudicated SCD in two large population-based cohorts: the Cardiovascular Health Study and the Atherosclerosis Risk in Communities study.

RESULTS: Over an average follow-up time of 11.7 years in Cardiovascular Health Study, there were 199 (3.6\%) cases of SCD among 5556 participants. In Atherosclerosis Risk in Communities study, over 12.6 years, there were 227 (1.5\%) cases of SCD among 15,633 participants. In both cohorts, there was a trend toward decreased SCD with taller height. In fixed effects meta-analysis, the pooled hazard ratio per 10 cm of height was 0.84; 95\% confidence interval, 0.73-0.98; P~= .03. The association of increased height with lower risk of SCD was slightly attenuated after inclusion of risk factors associated with height, such as hypertension and left ventricular hypertrophy. The association appeared stronger among men than women in both cohorts.

CONCLUSIONS: In two population-based prospective cohorts of different ages, greater height was associated with lower risk of SCD.

}, keywords = {Adult, Aged, Atherosclerosis, Body Height, Coronary Disease, Death, Sudden, Cardiac, Female, Humans, Hypertension, Incidence, Male, Middle Aged, Population Surveillance, Prospective Studies, Risk Factors}, issn = {1873-2585}, doi = {10.1016/j.annepidem.2013.11.008}, author = {Rosenberg, Michael A and Lopez, Faye L and B{\r u}zkov{\'a}, Petra and Adabag, Selcuk and Chen, Lin Y and Sotoodehnia, Nona and Kronmal, Richard A and Siscovick, David S and Alonso, Alvaro and Buxton, Alfred and Folsom, Aaron R and Mukamal, Kenneth J} } @article {6572, title = {Incidence of and risk factors for sick sinus~syndrome in the general population.}, journal = {J Am Coll Cardiol}, volume = {64}, year = {2014}, month = {2014 Aug 12}, pages = {531-8}, abstract = {

BACKGROUND: Little is known about the incidence of and risk factors for sick sinus syndrome (SSS), a common indication for pacemaker implantation.

OBJECTIVES: This study sought to describe the epidemiology of SSS.

METHODS: This analysis included 20,572 participants (mean baseline age 59 years, 43\% male) in the ARIC (Atherosclerosis Risk In Communities) study and the CHS (Cardiovascular Health Study), who at baseline were free of prevalent atrial fibrillation and pacemaker therapy, had a heart rate of >= 50 beats/min unless using beta blockers, and were identified as of white or black race. Incident SSS cases were identified by hospital discharge International Classification of Disease-revision 9-Clinical Modification code 427.81 and validated by medical record review.

RESULTS: During an average 17 years of follow-up, 291 incident SSS cases were identified (unadjusted rate 0.8 per 1,000 person-years). Incidence increased with age (hazard ratio [HR]: 1.73; 95\% confidence interval [CI]: 1.47 to 2.05 per 5-year increment), and blacks had a 41\% lower risk of SSS than whites (HR: 0.59; 95\% CI: 0.37 to 0.98). Incident SSS was associated with greater baseline body mass index, height, N-terminal pro-B-type natriuretic peptide, and cystatin C, with longer QRS interval, with lower heart rate, and with prevalent hypertension, right bundle branch block, and cardiovascular disease. We project that the annual number of new SSS cases in the United States will increase from 78,000 in 2012 to 172,000 in 2060.

CONCLUSIONS: Blacks have a lower risk of SSS than whites, and several cardiovascular risk factors were associated with incident SSS. With the aging of the population, the number of Americans with SSS will increase dramatically over the next 50 years.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Cohort Studies, European Continental Ancestry Group, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Population Surveillance, Prospective Studies, Risk Factors, Sick Sinus Syndrome}, issn = {1558-3597}, doi = {10.1016/j.jacc.2014.03.056}, author = {Jensen, Paul N and Gronroos, Noelle N and Chen, Lin Y and Folsom, Aaron R and deFilippi, Chris and Heckbert, Susan R and Alonso, Alvaro} } @article {6210, title = {The influence of sex on cardiovascular outcomes associated with diabetes among older black and white adults.}, journal = {J Diabetes Complications}, volume = {28}, year = {2014}, month = {2014 May-Jun}, pages = {316-22}, abstract = {

AIMS: It is unknown whether sex differences in the association of diabetes with cardiovascular outcomes vary by race. We examined sex differences in the associations of diabetes with incident congestive heart failure (CHF) and coronary heart disease (CHD) between older black and white adults.

METHODS: We analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort study of community-dwelling individuals aged >=65 from four US counties. We included 4817 participants (476 black women, 279 black men, 2447 white women and 1625 white men). We estimated event rates and multivariate-adjusted hazard ratios for incident CHF, CHD, and all-cause mortality by Cox regression and competing risk analyses.

RESULTS: Over a median follow-up of 12.5years, diabetes was more strongly associated with CHF among black women (HR, 2.42 [95\% CI, 1.70-3.40]) than black men (1.39 [0.83-2.34]); this finding did not reach statistical significance (P for interaction=0.08). Female sex conferred a higher risk for a composite outcome of CHF and CHD among black participants (2.44 [1.82-3.26]) vs. (1.44 [0.97-2.12]), P for interaction=0.03). There were no significant sex differences in the HRs associated with diabetes for CHF among whites, or for CHD or all-cause mortality among blacks or whites. The three-way interaction between sex, race, and diabetes on risk of cardiovascular outcomes was not significant (P=0.07).

CONCLUSIONS: Overall, sex did not modify the cardiovascular risk associated with diabetes among older black or white adults. However, our results suggest that a possible sex interaction among older blacks merits further study.

}, keywords = {African Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Coronary Disease, Diabetes Complications, European Continental Ancestry Group, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Prospective Studies, Regression Analysis, Retrospective Studies, Risk Factors, Sex Factors, Survival Rate}, issn = {1873-460X}, doi = {10.1016/j.jdiacomp.2013.12.004}, author = {Vimalananda, Varsha G and Biggs, Mary L and Rosenzweig, James L and Carnethon, Mercedes R and Meigs, James B and Thacker, Evan L and Siscovick, David S and Mukamal, Kenneth J} } @article {6148, title = {Metabolic syndrome and risk of incident peripheral artery disease: the cardiovascular health study.}, journal = {Hypertension}, volume = {63}, year = {2014}, month = {2014 Feb}, pages = {413-9}, abstract = {

Prior studies evaluating metabolic syndrome (MetS) and incident peripheral artery disease (PAD) have been limited by use of modified MetS criteria and restriction to clinical PAD end points. We investigated MetS and risk of developing a low ankle-brachial index (ABI) and clinical PAD in the Cardiovascular Health Study, a population-based cohort of adults aged >=65 years. Participants with MetS met at least 3 of 5 Adult Treatment Panel III criteria. Baseline C-reactive protein-MetS or fibrinogen-MetS were defined as presence of 3 of 6 components, with elevated C-reactive protein (>3 mg/L) or fibrinogen (>341 mg/dL) as a sixth component. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among a subset of 1899 individuals with 2 ABI measurements 6 years apart. Over a median follow-up of 13.7 years, 4632 individuals were followed up for clinical PAD, defined as revascularization or diagnosed claudication. Adult Treatment Panel III MetS was associated with both incident low ABI (risk ratio, 1.26; 95\% confidence interval [CI], 1.00-1.58) and clinical PAD (hazard ratio, 1.47; 95\% CI, 1.11-1.94). Incorporating C-reactive protein or fibrinogen into Adult Treatment Panel III criteria identified an additional 16\% to 20\% of individuals as having MetS, and both C-reactive protein-MetS and fibrinogen-MetS were associated with incident low ABI (risk ratio, 1.36; 95\% CI, 1.07-1.72 and risk ratio, 1.43; 95\% CI, 1.13-1.81, respectively) and clinical PAD (hazard ratio, 1.56; 95\% CI, 1.17-2.08 and hazard ratio, 1.55; 95\% CI, 1.17-2.07, respectively). Among Adult Treatment Panel III MetS criteria, risk of PAD was most strongly associated with hypertension.

}, keywords = {Aged, Ankle Brachial Index, C-Reactive Protein, Female, Fibrinogen, Follow-Up Studies, Humans, Incidence, Longitudinal Studies, Male, Metabolic Syndrome, Peripheral Arterial Disease, Prevalence, Risk Factors, Vasculitis}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.113.01925}, author = {Garg, Parveen K and Biggs, Mary L and Carnethon, Mercedes and Ix, Joachim H and Criqui, Michael H and Britton, Kathryn A and Djouss{\'e}, Luc and Sutton-Tyrrell, Kim and Newman, Anne B and Cushman, Mary and Mukamal, Kenneth J} } @article {6609, title = {Plasma phospholipid trans-fatty acids levels, cardiovascular diseases, and total mortality: the cardiovascular health study.}, journal = {J Am Heart Assoc}, volume = {3}, year = {2014}, month = {2014 Aug}, abstract = {

BACKGROUND: While self-reported trans-fatty acid (TFA) consumption is linked to coronary heart disease (CHD), relationships between objective biomarkers of TFA subtypes (t-16:1n9, total t-18:1, and cis/trans-(c/t-), t/c- and t/t-18:2) and cardiovascular disease (CVD) or total mortality are not well established.

METHODS AND RESULTS: We evaluated 2742 adults in the Cardiovascular Health Study, aged 74{\textpm}5 years and free of prevalent CVD, with plasma phospholipid TFA measures in 1992. Incident fatal and nonfatal CHD events, CVD and non-CVD mortality, and total mortality were centrally adjudicated through 2010. Risks were assessed using Cox proportional hazards. During 31 494 person-years, 1735 total deaths and 639 total CHD events occurred. In the multivariate model including mutual adjustment for the 5 TFA subtypes, circulating t/t-18:2 was associated with higher total mortality (extreme quintile hazard ratio (HR)=1.23, 95\% CI=1.04 to 1.44, P-trend=0.01), CVD mortality (HR=1.40, 95\% CI=1.05 to 1.86, P-trend=0.02), and total CHD (HR=1.39, 95\% CI=1.06 to 1.83, P-trend=0.01). t/c-18:2 was positively related to total mortality (HR=1.19, P-trend=0.05), total CHD (HR=1.67, P-trend=0.002), and nonfatal CHD (HR=2.06, P-trend=0.002) after mutual adjustment; these associations were insignificant without mutual adjustment. Neither t-16:1n9 nor t-18:1 was significantly associated with total mortality or CVD, nor was c/t-18:2 if we excluded early cases.

CONCLUSIONS: Among circulating TFAs, t/t-18:2 was most adversely associated with total mortality, mainly due to the increased risk of CVD. t/c-18:2 was also positively associated with total mortality and CHD, but only after adjustment for other TFAs. These results highlight the need for further investigation of dietary sources, nondietary determinants, and health effects of specific TFA subtypes, especially t-18:2 isomers.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cardiovascular Diseases, Cohort Studies, Dietary Fats, Female, Follow-Up Studies, Humans, Incidence, Male, Mortality, Phospholipids, Prognosis, Proportional Hazards Models, Prospective Studies, Trans Fatty Acids}, issn = {2047-9980}, doi = {10.1161/JAHA.114.000914}, author = {Wang, Qianyi and Imamura, Fumiaki and Lemaitre, Rozenn N and Rimm, Eric B and Wang, Molin and King, Irena B and Song, Xiaoling and Siscovick, David and Mozaffarian, Dariush} } @article {6625, title = {Ratio of urine albumin to creatinine attenuates the association of dementia with hip fracture risk.}, journal = {J Clin Endocrinol Metab}, volume = {99}, year = {2014}, month = {2014 Nov}, pages = {4116-23}, abstract = {

CONTEXT: Microvascular disease is a leading cause of cognitive impairment. Approximately 50\% of people with a hip fracture have cognitive impairment.

OBJECTIVE: We tested the hypothesis that microvascular diseases of the brain (lacunar infarcts and white matter disease [WMD]), kidney (albuminuria [>= 30 mg/g creatinine] and albumin creatinine ratio [ACR]), and eye (retinal vascular disorders) attenuate the association of cognitive impairment with hip fracture risk.

SETTING: The Cardiovascular Health Cognition Study.

PATIENTS: Three thousand, one-hundred six participants (mean age, \~{} 79 y; 8.84 y median follow-up) with cognitive testing. Subsets received ACR testing (n=2389), brain magnetic resonance imaging scans (n = 2094), and retinal photography (n = 1098).

MAIN OUTCOME MEASURE: Incident hip fracture.

RESULTS: There were 488 participants (16\%) with mild cognitive impairment (MCI) and 564 (18\%) with dementia. There were 337 incident hip fractures, of which 19\% occurred in participants with MCI and 26\% in participants with dementia. Adjusted hazard ratios (HR) and 95\% confidence interval for hip fracture in participants with MCI were 2.45 (1.67-3.61) and for dementia 2.35 (1.57-3.52). With doubling of ACR, the HR for fracture was attenuated in participants with dementia compared with participants with normal cognition [interaction HR 0.70 (0.55-0.91)]. No such effect was found in participants with MCI. Albuminuria, lacunar infarcts, WMD, and retinal vascular disease (RVD) did not modify the association of dementia or MCI with hip fracture risk.

CONCLUSIONS: ACR attenuates part of the risk of hip fracture in people with dementia, suggesting that these disorders share a common pathogenesis.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Creatinine, Dementia, Female, Hip Fractures, Humans, Incidence, Magnetic Resonance Imaging, Male, Mild Cognitive Impairment, Neuropsychological Tests, Prospective Studies, Risk}, issn = {1945-7197}, doi = {10.1210/jc.2014-2409}, author = {B{\r u}zkov{\'a}, Petra and Barzilay, Joshua I and Fink, Howard A and Robbins, John A and Cauley, Jane A and Fitzpatrick, Annette L} } @article {6137, title = {Relations of plasma total and high-molecular-weight adiponectin to new-onset heart failure in adults >=65 years of age (from the Cardiovascular Health study).}, journal = {Am J Cardiol}, volume = {113}, year = {2014}, month = {2014 Jan 15}, pages = {328-34}, abstract = {

Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine{\textquoteright}s association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged >=65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95\% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95\% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.

}, keywords = {Adiponectin, Age of Onset, Aged, Biomarkers, Cross-Sectional Studies, Echocardiography, Doppler, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Prognosis, Prospective Studies, Recurrence, Severity of Illness Index, United States, Ventricular Function, Left}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2013.09.027}, author = {Karas, Maria G and Benkeser, David and Arnold, Alice M and Bartz, Traci M and Djouss{\'e}, Luc and Mukamal, Kenneth J and Ix, Joachim H and Zieman, Susan J and Siscovick, David S and Tracy, Russell P and Mantzoros, Christos S and Gottdiener, John S and deFilippi, Christopher R and Kizer, Jorge R} } @article {6335, title = {Residential relocation by older adults in response to incident cardiovascular health events: a case-crossover analysis.}, journal = {J Environ Public Health}, volume = {2014}, year = {2014}, month = {2014}, pages = {951971}, abstract = {

OBJECTIVE: We use a case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new home address.

METHODS: We conducted an ambidirectional case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new address using data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults from four U.S. sites beginning in 1989. Relocation was assessed twice a year during follow-up. Event occurrences were classified as present or absent for the period preceding the first reported move, as compared with an equal length of time immediately prior to and following this period.

RESULTS: Older adults (65+) that experience incident cardiovascular disease had an increased probability of reporting a change of residence during the following year (OR 1.6, 95\% confidence interval (CI) = 1.2-2.1). Clinical conditions associated with relocation included stroke (OR: 2.0, 95\% CI: 1.2-3.3), angina (OR: 1.6, 95\% CI: 1.0-2.6), and congestive heart failure (OR: 1.5, 95\% CI: 1.0-2.1).

CONCLUSIONS: Major incident cardiovascular disease may increase the probability of residential relocation in older adults. Case-crossover analyses represent an opportunity to investigate triggering events, but finer temporal resolution would be crucial for future research on residential relocations.

}, keywords = {Aged, Cardiovascular Diseases, Cross-Over Studies, Female, Humans, Incidence, Life Change Events, Logistic Models, Longitudinal Studies, Male, Prospective Studies, Residence Characteristics, United States}, issn = {1687-9813}, doi = {10.1155/2014/951971}, author = {Lovasi, Gina S and Richardson, John M and Rodriguez, Carlos J and Kop, Willem J and Ahmed, Ali and Brown, Arleen F and Greenlee, Heather and Siscovick, David S} } @article {9409, title = {A self-report risk index to predict occurrence of dementia in three independent cohorts of older adults: the ANU-ADRI.}, journal = {PLoS One}, volume = {9}, year = {2014}, month = {2014}, pages = {e86141}, abstract = {

BACKGROUND AND AIMS: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer{\textquoteright}s disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts.

METHODS: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age >=53 years), the Kungsholmen Project (KP) (n = 905, age >=75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age >=65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index.

RESULTS: For the ANU-ADRI using available data, the MAP study c-statistic was 0{\textperiodcentered}637 (95\% CI 0{\textperiodcentered}596-0{\textperiodcentered}678), for the KP study it was 0{\textperiodcentered}740 (0{\textperiodcentered}712-0{\textperiodcentered}768) and for the CVHS it was 0{\textperiodcentered}733 (0{\textperiodcentered}691-0{\textperiodcentered}776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95\% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625).

CONCLUSION: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up.

}, keywords = {Adult, Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Female, Humans, Incidence, Male, Middle Aged, Risk, ROC Curve, Self Report}, issn = {1932-6203}, doi = {10.1371/journal.pone.0086141}, author = {Anstey, Kaarin J and Cherbuin, Nicolas and Herath, Pushpani M and Qiu, Chengxuan and Kuller, Lewis H and Lopez, Oscar L and Wilson, Robert S and Fratiglioni, Laura} } @article {6338, title = {Separate prediction of intracerebral hemorrhage and ischemic stroke.}, journal = {Neurology}, volume = {82}, year = {2014}, month = {2014 May 20}, pages = {1804-12}, abstract = {

OBJECTIVES: To develop and validate 10-year cumulative incidence functions of intracerebral hemorrhage (ICH) and ischemic stroke (IS).

METHODS: We used data on 27,493 participants from 3 population-based cohort studies: the Atherosclerosis Risk in Communities Study, median age 54 years, 45\% male, median follow-up 20.7 years; the Rotterdam Study, median age 68 years, 38\% male, median follow-up 14.3 years; and the Cardiovascular Health Study, median age 71 years, 41\% male, median follow-up 12.8 years. Among these participants, 325 ICH events, 2,559 IS events, and 9,909 nonstroke deaths occurred. We developed 10-year cumulative incidence functions for ICH and IS using stratified Cox regression and competing risks analysis. Basic models including only established nonlaboratory risk factors were extended with diastolic blood pressure, total cholesterol/high-density lipoprotein cholesterol ratio, body mass index, waist-to-hip ratio, and glomerular filtration rate. The cumulative incidence functions{\textquoteright} performances were cross-validated in each cohort separately by Harrell C-statistic and calibration plots.

RESULTS: High total cholesterol/high-density lipoprotein cholesterol ratio decreased the ICH rates but increased IS rates (p for difference across stroke types <0.001). For both the ICH and IS models, C statistics increased more by model extension in the Atherosclerosis Risk in Communities and Cardiovascular Health Study cohorts. Improvements in C statistics were reproduced by cross-validation. Models were well calibrated in all cohorts. Correlations between 10-year ICH and IS risks were moderate in each cohort.

CONCLUSIONS: We developed and cross-validated cumulative incidence functions for separate prediction of 10-year ICH and IS risk. These functions can be useful to further specify an individual{\textquoteright}s stroke risk.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Body Mass Index, Brain Ischemia, Cholesterol, Female, Humans, Incidence, Intracranial Hemorrhages, Male, Middle Aged, Models, Statistical, Predictive Value of Tests, Risk Assessment, Risk Factors, Stroke}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000000427}, author = {Ferket, Bart S and van Kempen, Bob J H and Wieberdink, Renske G and Steyerberg, Ewout W and Koudstaal, Peter J and Hofman, Albert and Shahar, Eyal and Gottesman, Rebecca F and Rosamond, Wayne and Kizer, Jorge R and Kronmal, Richard A and Psaty, Bruce M and Longstreth, W T and Mosley, Thomas and Folsom, Aaron R and Hunink, M G Myriam and Ikram, M Arfan} } @article {6243, title = {Serum carboxymethyl-lysine, disability, and frailty in older persons: the Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {69}, year = {2014}, month = {2014 Jun}, pages = {710-6}, abstract = {

BACKGROUND: Advanced glycation endproducts are biologically active compounds that accumulate in disordered metabolism and normal aging. Carboxymethyl-lysine (CML), a ubiquitous human advanced glycation endproduct, has been associated with age-related conditions and mortality. Our objective was to ascertain the relationship between CML and geriatric outcomes (disability and frailty) in a large cohort of older men and women.

METHODS: In 1996-1997, serum CML was measured in 3,373 Cardiovascular Health Study participants (mean age 78.1 {\textpm} 4.8 years). Disability, defined as difficulty in any of six activities of daily living, was assessed every 6-12 months for 14 years. Frailty was defined according to five standard criteria at the 1996-1997 visit. Cox proportional hazard models estimated the relationship between CML and incident disability (N = 2,643). Logistic regression models estimated the relationship between CML and prevalent frailty.

RESULTS: Adjusting for multiple potential confounders, higher CML was associated with incident disability (hazard ratio per standard deviation [225 ng/mL] increase: 1.05, 95\% CI 1.01-1.11). In men, odds of frailty increased with higher CML values (odds ratio = 1.30 per standard deviation, 95\% CI 1.14-1.48), but the relationship was attenuated by adjustment for cognitive status, kidney function, and arthritis. CML was not associated with frailty in women.

CONCLUSIONS: Higher serum CML levels in late life are associated with incident disability and prevalent frailty. Further work is needed to understand CML{\textquoteright}s value as a risk stratifier, biomarker, or target for interventions that promote healthy aging.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Aging, Biomarkers, Cardiac Rehabilitation, Cardiovascular Diseases, Disabled Persons, Female, Follow-Up Studies, Frail Elderly, Health Status, Humans, Incidence, Lysine, Male, Prevalence, Prognosis, Retrospective Studies, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glt155}, author = {Whitson, Heather E and Arnold, Alice M and Yee, Laura M and Mukamal, Kenneth J and Kizer, Jorge R and Djouss{\'e}, Luc and Ix, Joachim H and Siscovick, David and Tracy, Russell P and Thielke, Stephen M and Hirsch, Calvin and Newman, Anne B and Zieman, Susan} } @article {6398, title = {Systolic and diastolic blood pressure, incident cardiovascular events, and death in elderly persons: the role of functional limitation in the Cardiovascular Health Study.}, journal = {Hypertension}, volume = {64}, year = {2014}, month = {2014 Sep}, pages = {472-80}, abstract = {

Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78{\textpm}5 and 21\% reported limitation in >=1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95\% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP <=65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of <=65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.

}, keywords = {Activities of Daily Living, African Continental Ancestry Group, Aged, Aged, 80 and over, Blood Pressure, Cardiovascular Diseases, Diastole, European Continental Ancestry Group, Female, Follow-Up Studies, Gait, Heart Rate, Humans, Incidence, Longitudinal Studies, Male, Risk Factors, Survival Rate, Systole}, issn = {1524-4563}, doi = {10.1161/HYPERTENSIONAHA.114.03831}, author = {Peralta, Carmen A and Katz, Ronit and Newman, Anne B and Psaty, Bruce M and Odden, Michelle C} } @article {6594, title = {Telomere length and the risk of atrial fibrillation: insights into the role of biological versus chronological aging.}, journal = {Circ Arrhythm Electrophysiol}, volume = {7}, year = {2014}, month = {2014 Dec}, pages = {1026-32}, abstract = {

BACKGROUND: Advanced age is the most important risk factor for atrial fibrillation (AF); however, the mechanism remains unknown. Telomeres, regions of DNA that shorten with cell division, are considered reliable markers of biological aging. We sought to examine the association between leukocyte telomere length (LTL) and incident AF in a large population-based cohort using direct LTL measurements and genetic data. To further explore our findings, we compared atrial cell telomere length and LTL in cardiac surgery patients.

METHODS AND RESULTS: Mean LTL and the TERT rs2736100 single nucleotide polymorphism were assessed as predictors of incident AF in the Cardiovascular Health Study (CHS). Among the surgical patients, within subject comparison of atrial cell telomere length versus LTL was assessed. Among 1639 CHS participants, we observed no relationship between mean LTL and incident AF before and after adjustment for potential confounders (adjusted hazard ratio, 1.09; 95\% confidence interval: 0.92-1.29; P=0.299); chronologic age remained strongly associated with AF in the same model. No association was observed between the TERT rs2736100 single nucleotide polymorphism and incident AF (adjusted hazard ratio: 0.95; 95\% confidence interval: 0.88-1.04; P=0.265). In 35 cardiac surgery patients (26 with AF), atrial cell telomere length was longer than LTL (1.19 {\textpm} 0.20 versus 1.02 {\textpm} 0.25 [T/S ratio], P<0.001), a finding that remained consistent within the AF subgroup.

CONCLUSIONS: Our study revealed no evidence of an association between LTL and incident AF and no evidence of relative atrial cell telomere shortening in AF. Chronological aging independent of biological markers of aging is the primary risk factor for AF.

}, keywords = {Age Factors, Aged, Aging, Atrial Fibrillation, California, Cardiac Surgical Procedures, Cellular Senescence, Cross-Sectional Studies, Female, Genetic Predisposition to Disease, Humans, Incidence, Leukocytes, Male, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Telomerase, Telomere, Time Factors}, issn = {1941-3084}, doi = {10.1161/CIRCEP.114.001781}, author = {Roberts, Jason D and Dewland, Thomas A and Longoria, James and Fitzpatrick, Annette L and Ziv, Elad and Hu, Donglei and Lin, Jue and Glidden, David V and Psaty, Bruce M and Burchard, Esteban G and Blackburn, Elizabeth H and Olgin, Jeffrey E and Heckbert, Susan R and Marcus, Gregory M} } @article {6277, title = {Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.}, journal = {Clin Endocrinol (Oxf)}, volume = {81}, year = {2014}, month = {2014 Nov}, pages = {746-53}, abstract = {

OBJECTIVE: Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men.

DESIGN: Cohort study.

PARTICIPANTS: Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010.

MEASUREMENTS: Adjudicated ischaemic stroke.

RESULTS: Among 1032 men (mean age 76, range 66-97), followed for a median of 10~years, 114 had an incident ischaemic stroke. Total T and free T were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke (P~=~0{\textperiodcentered}006) in analyses adjusted for stroke risk factors. The lowest risk of stroke was at DHT levels of 50-75~ng/dl, with greater risk of stroke at DHT levels above 75~ng/dl or below 50~ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischaemic stroke with HR 0{\textperiodcentered}77 (95\% CI, 0{\textperiodcentered}61, 0{\textperiodcentered}98) per standard deviation in analyses adjusted for stroke risk factors.

CONCLUSIONS: Dihydrotestosterone had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify whether there is an optimal androgen range associated with the least risk of adverse outcomes in elderly men.

}, keywords = {Aged, Aged, 80 and over, Brain Ischemia, Cardiovascular Physiological Phenomena, Dihydrotestosterone, Health, Humans, Incidence, Longitudinal Studies, Male, Stroke, Testosterone}, issn = {1365-2265}, doi = {10.1111/cen.12452}, author = {Shores, Molly M and Arnold, Alice M and Biggs, Mary L and Longstreth, W T and Smith, Nicholas L and Kizer, Jorge R and Cappola, Anne R and Hirsch, Calvin H and Marck, Brett T and Matsumoto, Alvin M} } @article {6278, title = {Testosterone, dihydrotestosterone, and incident cardiovascular disease and mortality in the cardiovascular health study.}, journal = {J Clin Endocrinol Metab}, volume = {99}, year = {2014}, month = {2014 Jun}, pages = {2061-8}, abstract = {

CONTEXT: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this.

OBJECTIVE: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality.

DESIGN: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection.

MAIN OUTCOME: The main outcomes were incident CVD and all-cause mortality.

RESULTS: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both).

CONCLUSIONS: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cause of Death, Dihydrotestosterone, Humans, Incidence, Longitudinal Studies, Male, Mortality, Residence Characteristics, Risk Factors, Testosterone}, issn = {1945-7197}, doi = {10.1210/jc.2013-3576}, author = {Shores, Molly M and Biggs, Mary L and Arnold, Alice M and Smith, Nicholas L and Longstreth, W T and Kizer, Jorge R and Hirsch, Calvin H and Cappola, Anne R and Matsumoto, Alvin M} } @article {6553, title = {Thyroid antibody status, subclinical hypothyroidism, and the risk of coronary heart disease: an individual participant data analysis.}, journal = {J Clin Endocrinol Metab}, volume = {99}, year = {2014}, month = {2014 Sep}, pages = {3353-62}, abstract = {

CONTEXT: Subclinical hypothyroidism has been associated with increased risk of coronary heart disease (CHD), particularly with thyrotropin levels of 10.0 mIU/L or greater. The measurement of thyroid antibodies helps predict the progression to overt hypothyroidism, but it is unclear whether thyroid autoimmunity independently affects CHD risk.

OBJECTIVE: The objective of the study was to compare the CHD risk of subclinical hypothyroidism with and without thyroid peroxidase antibodies (TPOAbs).

DATA SOURCES AND STUDY SELECTION: A MEDLINE and EMBASE search from 1950 to 2011 was conducted for prospective cohorts, reporting baseline thyroid function, antibodies, and CHD outcomes.

DATA EXTRACTION: Individual data of 38 274 participants from six cohorts for CHD mortality followed up for 460 333 person-years and 33 394 participants from four cohorts for CHD events.

DATA SYNTHESIS: Among 38 274 adults (median age 55 y, 63\% women), 1691 (4.4\%) had subclinical hypothyroidism, of whom 775 (45.8\%) had positive TPOAbs. During follow-up, 1436 participants died of CHD and 3285 had CHD events. Compared with euthyroid individuals, age- and gender-adjusted risks of CHD mortality in subclinical hypothyroidism were similar among individuals with and without TPOAbs [hazard ratio (HR) 1.15, 95\% confidence interval (CI) 0.87-1.53 vs HR 1.26, CI 1.01-1.58, P for interaction = .62], as were risks of CHD events (HR 1.16, CI 0.87-1.56 vs HR 1.26, CI 1.02-1.56, P for interaction = .65). Risks of CHD mortality and events increased with higher thyrotropin, but within each stratum, risks did not differ by TPOAb status.

CONCLUSIONS: CHD risk associated with subclinical hypothyroidism did not differ by TPOAb status, suggesting that biomarkers of thyroid autoimmunity do not add independent prognostic information for CHD outcomes.

}, keywords = {Adult, Aged, Aged, 80 and over, Autoantibodies, Coronary Disease, Female, Humans, Hypothyroidism, Incidence, Male, Middle Aged, Prevalence, Prognosis, Risk Factors, Seroepidemiologic Studies, Severity of Illness Index, Young Adult}, issn = {1945-7197}, doi = {10.1210/jc.2014-1250}, author = {Collet, Tinh-Hai and Bauer, Douglas C and Cappola, Anne R and Asvold, Bj{\o}rn O and Weiler, Stefan and Vittinghoff, Eric and Gussekloo, Jacobijn and Bremner, Alexandra and den Elzen, Wendy P J and Maciel, Rui M B and Vanderpump, Mark P J and Cornuz, Jacques and D{\"o}rr, Marcus and Wallaschofski, Henri and Newman, Anne B and Sgarbi, Jos{\'e} A and Razvi, Salman and V{\"o}lzke, Henry and Walsh, John P and Aujesky, Drahomir and Rodondi, Nicolas} } @article {6235, title = {Troponin T, NT-proBNP, and venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Vasc Med}, volume = {19}, year = {2014}, month = {2014 Feb}, pages = {33-41}, abstract = {

Increased levels of plasma troponins and natriuretic peptides are markers of cardiac dysfunction associated with increased risk of cardiovascular disease. Little information exists on cardiac dysfunction and occurrence of venous thromboembolism (VTE). In two prospective epidemiological cohorts, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with VTE occurrence. The Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS) measured plasma TnT and NT-proBNP in 13,719 men or women with no history of venous thrombosis, coronary heart disease, or heart failure and followed them for approximately 10 years for VTE occurrence (n = 348 VTEs). In both ARIC and CHS, TnT was associated positively with incidence of total VTE and provoked VTE, but not with unprovoked VTE: age, race, and sex-adjusted hazard ratios for total VTE in the pooled analysis were 1.00, 0.85, 1.36, 1.51, and 1.98 (p-trend <0.0001) across five categories of TnT. In contrast, the association of NT-proBNP with VTE was positive in ARIC (hazard ratios approximately 2.5-fold for the highest versus lowest NT-proBNP quintiles), but non-existent in CHS.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Prospective Studies, Risk Factors, Troponin T, Venous Thromboembolism}, issn = {1477-0377}, doi = {10.1177/1358863X14520869}, author = {Folsom, Aaron R and Lutsey, Pamela L and Nambi, Vijay and deFilippi, Christopher R and Heckbert, Susan R and Cushman, Mary and Ballantyne, Christie M} } @article {7017, title = {Vitamin D and the risk of dementia and Alzheimer disease.}, journal = {Neurology}, volume = {83}, year = {2014}, month = {2014 Sep 2}, pages = {920-8}, abstract = {

OBJECTIVE: To determine whether low vitamin D concentrations are associated with an increased risk of incident all-cause dementia and Alzheimer disease.

METHODS: One thousand six hundred fifty-eight elderly ambulatory adults free from dementia, cardiovascular disease, and stroke who participated in the US population-based Cardiovascular Health Study between 1992-1993 and 1999 were included. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were determined by liquid chromatography-tandem mass spectrometry from blood samples collected in 1992-1993. Incident all-cause dementia and Alzheimer disease status were assessed during follow-up using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria.

RESULTS: During a mean follow-up of 5.6 years, 171 participants developed all-cause dementia, including 102 cases of Alzheimer disease. Using Cox proportional hazards models, the multivariate adjusted hazard ratios (95\% confidence interval [CI]) for incident all-cause dementia in participants who were severely 25(OH)D deficient (<25 nmol/L) and deficient (>=25 to <50 nmol/L) were 2.25 (95\% CI: 1.23-4.13) and 1.53 (95\% CI: 1.06-2.21) compared to participants with sufficient concentrations (>=50 nmol/L). The multivariate adjusted hazard ratios for incident Alzheimer disease in participants who were severely 25(OH)D deficient and deficient compared to participants with sufficient concentrations were 2.22 (95\% CI: 1.02-4.83) and 1.69 (95\% CI: 1.06-2.69). In multivariate adjusted penalized smoothing spline plots, the risk of all-cause dementia and Alzheimer disease markedly increased below a threshold of 50 nmol/L.

CONCLUSION: Our results confirm that vitamin D deficiency is associated with a substantially increased risk of all-cause dementia and Alzheimer disease. This adds to the ongoing debate about the role of vitamin D in nonskeletal conditions.

}, keywords = {Aged, Alzheimer Disease, Dementia, Female, Follow-Up Studies, Humans, Incidence, Male, Proportional Hazards Models, Risk Factors, United States, Vitamin D, Vitamin D Deficiency}, issn = {1526-632X}, doi = {10.1212/WNL.0000000000000755}, author = {Littlejohns, Thomas J and Henley, William E and Lang, Iain A and Annweiler, Cedric and Beauchet, Olivier and Chaves, Paulo H M and Fried, Linda and Kestenbaum, Bryan R and Kuller, Lewis H and Langa, Kenneth M and Lopez, Oscar L and Kos, Katarina and Soni, Maya and Llewellyn, David J} } @article {6564, title = {What do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.}, journal = {J Am Soc Echocardiogr}, volume = {27}, year = {2014}, month = {2014 Sep}, pages = {998-1005.e2}, abstract = {

BACKGROUND: The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults.

METHODS: Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell{\textquoteright}s c-statistic were calculated.

RESULTS: In 4,384 Cardiovascular Health Study participants (61\% women, 14\% black; mean baseline age, 72~{\textpm}~5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI~= 0.062, P~=~.015, and NRI~= 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMT~did not result in a significant NRI for either outcome, it was significant among those without incident disease.

CONCLUSIONS: In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events.

}, keywords = {Aged, Cardiovascular Diseases, Carotid Intima-Media Thickness, Carotid Stenosis, Comorbidity, Female, Humans, Incidence, Longitudinal Studies, Male, Reproducibility of Results, Risk Factors, Sensitivity and Specificity, Stroke, Survival Rate}, issn = {1097-6795}, doi = {10.1016/j.echo.2014.06.013}, author = {Gardin, Julius M and Bartz, Traci M and Polak, Joseph F and O{\textquoteright}Leary, Daniel H and Wong, Nathan D} } @article {6666, title = {Association of Fetuin-A With Incident Fractures in Community-Dwelling Older Adults: The Cardiovascular Health Study.}, journal = {J Bone Miner Res}, volume = {30}, year = {2015}, month = {2015 Aug}, pages = {1394-402}, abstract = {

Fetuin-A, a serum protein that regulates calcium mineralization, has been associated with bone mineral density (BMD) in several cross-sectional human studies, suggesting a possible beneficial effect on clinically important measures of bone health. Fetuin-A and incidence of subsequent fracture was assessed in 4714 men and women >=65 years of age. Proportional hazards models were used to estimate risk of incident hip (hospital discharge ICD-9 codes) and composite fracture (hip, pelvis, humerus, or proximal forearm; hospital discharge ICD-9 codes and Medicare claims data). A total of 576 participants had an incident hip fracture (median follow-up 11.2 years) and 768 had an incident composite fracture (median follow-up 6.9 years). In unadjusted analyses, there was no association between fetuin-A (per SD increase) and risk of hip fracture (hazard ratio [HR], 0.96; 95\% CI, 0.88 to 1.05) or composite fracture (HR, 0.99; 95\% CI, 0.92 to 1.06). Results were not significantly changed after adjustment for potential confounding variables. Analyses modeling fetuin-A in quartiles or within a subset with available BMD measures also showed no statistically significant association with risk of hip or composite fracture. Though fetuin-A was positively associated with areal BMD in partially adjusted models (total hip: β, 0.013 g/cm(2) ; 95\% CI, 0.005 to 0.021; femoral neck: β, 0.011 g/cm(2) ; 95\% CI, 0.004 to 0.018; and lumbar spine: β, 0.007 g/cm(2) ; 95\% CI, 0.001 to 0.028), these associations were no longer significant after further adjustment for BMI and in final multivariate models. In this large sample of community-dwelling older adults, a small positive association between fetuin-A and areal BMD appeared attributable to confounding variables and we found no evidence of an association between fetuin-A and risk of clinical fracture.

}, keywords = {Adult, Aged, Aged, 80 and over, alpha-2-HS-Glycoprotein, Bone Density, Cross-Sectional Studies, Female, Follow-Up Studies, Fractures, Bone, Humans, Incidence, Male, Models, Biological}, issn = {1523-4681}, doi = {10.1002/jbmr.2475}, author = {Fink, Howard A and B{\r u}zkov{\'a}, Petra and Garimella, Pranav S and Mukamal, Kenneth J and Cauley, Jane A and Kizer, Jorge R and Barzilay, Joshua I and Jalal, Diana I and Ix, Joachim H} } @article {6768, title = {Burden of Comorbidities and Functional and Cognitive Impairments in Elderly Patients at the Initial Diagnosis of Heart Failure and Their Impact on Total Mortality: The Cardiovascular Health Study.}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jul}, pages = {542-50}, abstract = {

OBJECTIVES: The purpose of this study was to determine the prevalence of clinically relevant comorbidities and measures of physical and cognitive impairment in elderly persons with incident heart failure (HF).

BACKGROUND: Comorbidities and functional and cognitive impairments are common in the elderly and often associated with greater mortality risk.

METHODS: We examined the prevalence of 9 comorbidities and 4 measures of functional and cognitive impairments in 558 participants from the Cardiovascular Health Study who developed incident HF between 1990 and 2002. Participants were followed prospectively until mid-2008 to determine their mortality risk.

RESULTS: Mean age of participants was 79.2 {\textpm} 6.3 years with 52\% being men. Sixty percent of participants had >=3 comorbidities, and only 2.5\% had none. Twenty-two percent and 44\% of participants had >=1 activity of daily living (ADL) and >=1 instrumental activity of daily living (IADL) impaired respectively. Seventeen percent of participants had cognitive impairment (modified mini-mental state exam score <80, scores range between 0 and 100). During follow up, 504 participants died, with 1-, 5-, and 10-year mortality rates of 19\%, 56\%, and 83\%, respectively. In a multivariable-adjusted model, the following were significantly associated with greater total mortality risk: diabetes mellitus (hazard ratio [HR]: 1.64; 95\% confidence interval [CI]: 1.33 to 2.03), chronic kidney disease (HR: 1.32; 95\% CI: 1.07 to 1.62 for moderate disease; HR: 3.00; 95\% CI: 1.82 to 4.95 for severe), cerebrovascular disease (HR: 1.53; 95\% CI: 1.22 to 1.92), depression (HR: 1.44; 95\% CI: 1.09 to 1.90), functional impairment (HR: 1.30; 95\% CI: 1.04 to 1.63 for 1 IADL impaired; HR: 1.49; 95\% CI: 1.07 to 2.04 for >=2 IADL impaired), and cognitive impairment (HR: 1.33; 95\% CI: 1.02 to 1.73). Other comorbidities (hypertension, coronary heart disease, peripheral arterial disease, atrial fibrillation, and obstructive airway disease) and measures of functional impairments (ADLs and 15-ft walk time) were not associated with mortality.

CONCLUSIONS: Elderly patients with incident HF have a high burden of comorbidities and functional and cognitive impairments. Some of these conditions are associated with greater mortality risk.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Atrial Fibrillation, Cognition Disorders, Cohort Studies, Comorbidity, Coronary Disease, Female, Heart Failure, Humans, Hypertension, Incidence, Longitudinal Studies, Male, Peripheral Arterial Disease, Physical Fitness, Prevalence, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive}, issn = {2213-1787}, doi = {10.1016/j.jchf.2015.03.004}, author = {Murad, Khalil and Goff, David C and Morgan, Timothy M and Burke, Gregory L and Bartz, Traci M and Kizer, Jorge R and Chaudhry, Sarwat I and Gottdiener, John S and Kitzman, Dalane W} } @article {6810, title = {Coagulation factor~XII genetic variation, ex~vivo thrombin generation, and stroke risk in the elderly: results from the Cardiovascular Health Study.}, journal = {J Thromb Haemost}, volume = {13}, year = {2015}, month = {2015 Oct}, pages = {1867-77}, abstract = {

BACKGROUND: The relationships of thrombin generation (TG) with cardiovascular disease risk are underevaluated in population-based cohorts.

OBJECTIVES: To evaluate the relationships of TG influenced by the contact and tissue factor coagulation pathways ex~vivo with common single-nucleotide polymorphisms (SNPs) and incident cardiovascular disease and stroke.

PATIENTS/METHODS: We measured peak TG (pTG) in baseline plasma samples of Cardiovascular Health Study participants (n~=~5411), both with and without inhibitory anti-factor~XIa antibody (pTG/FXIa(-) ). We evaluated their associations with ~~50~000 SNPs by using the IBCv2 genotyping array, and with incident cardiovascular disease and stroke events over a median follow-up of 13.2~years.

RESULTS: The minor allele for an SNP in the FXII gene (F12), rs1801020, was associated with lower pTG in European-Americans (β~=~-~34.2~{\textpm}~3.5~nm; P~=~3.3~{\texttimes}~10(-22) ; minor allele frequency [MAF]~=~0.23) and African-Americans (β~=~-~31.1~{\textpm}~7.9~nm; P~=~9.0~{\texttimes} 10(-5) ; MAF~=~0.42). Lower FXIa-independent pTG (pTG/FXIa(-) ) was associated with the F12 rs1801020 minor allele, and higher pTG/FXIa(-) was associated with the ABO SNP rs657152 minor allele (β~=~16.3~nm; P~=~4.3~{\texttimes}~10(-9) ; MAF~=~0.37). The risk factor-adjusted ischemic stroke hazard ratios were 1.09 (95\% confidence interval CI~1.01-1.17; P~=~0.03) for pTG, 1.06 (95\% CI~0.98-1.15; P~=~0.17) for pTG/FXIa(-) , and 1.11 (95\% CI~1.02-1.21; P~=~0.02) for FXIa-dependent pTG (pTG/FXIa(+) ), per one standard deviation increment (n~=~834 ischemic strokes). In a multicohort candidate gene analysis, rs1801020 was not associated with incident ischemic stroke (β~=~-~0.02; standard error~=~0.08; P~=~0.81).

CONCLUSIONS: These results support the importance of contact activation pathway-dependent TG as a risk factor for ischemic stroke, and indicate the importance of F12 SNPs for TG ex~vivo and in~vivo.

}, keywords = {African Americans, Age Factors, Aged, Blood Coagulation, Brain Ischemia, European Continental Ancestry Group, Factor XII, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Incidence, Male, Phenotype, Polymorphism, Single Nucleotide, Prospective Studies, Risk Assessment, Risk Factors, Stroke, Thrombin, Time Factors, United States}, issn = {1538-7836}, doi = {10.1111/jth.13111}, author = {Olson, N C and Butenas, S and Lange, L A and Lange, E M and Cushman, M and Jenny, N S and Walston, J and Souto, J C and Soria, J M and Chauhan, G and Debette, S and Longstreth, W T and Seshadri, S and Reiner, A P and Tracy, R P} } @article {6769, title = {Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults: The Cardiovascular Health Study.}, journal = {JACC Heart Fail}, volume = {3}, year = {2015}, month = {2015 Jul}, pages = {520-8}, abstract = {

OBJECTIVES: The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults.

BACKGROUND: HF incurs high morbidity, mortality, and health care costs among adults >=65 years of age, which is the most rapidly growing segment of the U.S.

METHODS: We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity.

RESULTS: No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26\% and 22\% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95\% confidence interval [CI]: 0.63 to 0.86; leisure activity >=845 kcal/week vs. <845 kcal/week; HR: 0.78; 95\% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m(2), and not smoking were also independently associated with a lower risk of HF. Participants with >=4 healthy lifestyle factors had a 45\% (HR: 0.55; 95\% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed.

CONCLUSIONS: Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF.

}, keywords = {Aged, Alcohol Drinking, Cohort Studies, Diet, Female, Heart Failure, Humans, Incidence, Male, Motor Activity, Obesity, Proportional Hazards Models, Prospective Studies, Risk Factors, Sedentary Lifestyle, Smoking, United States}, issn = {2213-1787}, doi = {10.1016/j.jchf.2015.02.009}, author = {Del Gobbo, Liana C and Kalantarian, Shadi and Imamura, Fumiaki and Lemaitre, Rozenn and Siscovick, David S and Psaty, Bruce M and Mozaffarian, Dariush} } @article {6875, title = {Drug-Gene Interactions of Antihypertensive Medications and Risk of Incident Cardiovascular Disease: A Pharmacogenomics Study from the CHARGE Consortium.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0140496}, abstract = {

BACKGROUND: Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.

METHODS: Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).

RESULTS: Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction > 5.0{\texttimes}10-8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction >= 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.

}, keywords = {African Americans, Aged, Antihypertensive Agents, Cardiovascular Diseases, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Hypertension, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Treatment Outcome}, issn = {1932-6203}, doi = {10.1371/journal.pone.0140496}, author = {Bis, Joshua C and Sitlani, Colleen and Irvin, Ryan and Avery, Christy L and Smith, Albert Vernon and Sun, Fangui and Evans, Daniel S and Musani, Solomon K and Li, Xiaohui and Trompet, Stella and Krijthe, Bouwe P and Harris, Tamara B and Quibrera, P Miguel and Brody, Jennifer A and Demissie, Serkalem and Davis, Barry R and Wiggins, Kerri L and Tranah, Gregory J and Lange, Leslie A and Sotoodehnia, Nona and Stott, David J and Franco, Oscar H and Launer, Lenore J and St{\"u}rmer, Til and Taylor, Kent D and Cupples, L Adrienne and Eckfeldt, John H and Smith, Nicholas L and Liu, Yongmei and Wilson, James G and Heckbert, Susan R and Buckley, Brendan M and Ikram, M Arfan and Boerwinkle, Eric and Chen, Yii-Der Ida and de Craen, Anton J M and Uitterlinden, Andr{\'e} G and Rotter, Jerome I and Ford, Ian and Hofman, Albert and Sattar, Naveed and Slagboom, P Eline and Westendorp, Rudi G J and Gudnason, Vilmundur and Vasan, Ramachandran S and Lumley, Thomas and Cummings, Steven R and Taylor, Herman A and Post, Wendy and Jukema, J Wouter and Stricker, Bruno H and Whitsel, Eric A and Psaty, Bruce M and Arnett, Donna} } @article {6665, title = {Fibrosis-related biomarkers and large and small vessel disease: the Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {239}, year = {2015}, month = {2015 Apr}, pages = {539-46}, abstract = {

OBJECTIVE: Fibrosis has been implicated in a number of pathological, organ-based conditions of the liver, kidney, heart, and lungs. The objective of this study was to determine whether biomarkers of fibrosis are associated with vascular disease in the large and/or small vessels.

METHODS: We evaluated the associations of two circulating biomarkers of fibrosis, transforming growth factor-β (TGF-β) and procollagen type III N-terminal propeptide (PIIINP), with incident peripheral artery disease (PAD) and subclinical macrovascular (carotid intima-media thickness, flow-mediated vasodilation, ankle-brachial index, retinal vein diameter), and microvascular (retinal artery diameter and retinopathy) disease among older adults in the Cardiovascular Health Study. We measured TGF-β and PIIINP from samples collected in 1996 and ascertained clinical PAD through 2011. Measurements of large and small vessels were collected between 1996 and 1998.

RESULTS: After adjustment for sociodemographic, clinical, and biochemical risk factors, TGF-β was associated with incident PAD (hazard ratio [HR]~=~1.36 per doubling of TGF-β, 95\% confidence interval [CI]~=~1.04, 1.78) and retinal venular diameter (1.63~μm per doubling of TGF-β, CI~=~0.23, 3.02). PIIINP was not associated with incident PAD, but was associated with carotid intima-media thickness (0.102~mm per doubling of PIIINP, CI~=~0.029, 0.174) and impaired brachial artery reactivity (-0.20\% change per doubling of PIIINP, CI~=~-0.39,~-0.02). Neither TGF-β nor PIIINP were associated with retinal arteriolar diameter or retinopathy.

CONCLUSIONS: Serum concentrations of fibrosis-related biomarkers were associated with several measures of large vessel disease, including incident PAD, but not with small vessel disease. Fibrosis may contribute to large vessel atherosclerosis in older adults.

}, keywords = {Aged, Ankle Brachial Index, Biomarkers, Brachial Artery, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cross-Sectional Studies, Female, Fibrosis, Humans, Incidence, Male, Peptide Fragments, Peripheral Arterial Disease, Predictive Value of Tests, Procollagen, Prognosis, Prospective Studies, Retinal Diseases, Risk Factors, Transforming Growth Factor beta, United States, Vasodilation}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2015.02.020}, author = {Agarwal, Isha and Arnold, Alice and Glazer, Nicole L and Barasch, Eddy and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Gottdiener, John S and Ix, Joachim H and Jensen, Richard A and Kizer, Jorge R and Rimm, Eric B and Siscovick, David S and Tracy, Russell P and Wong, Tien Y and Mukamal, Kenneth J} } @article {6801, title = {Higher circulating adiponectin levels are associated with increased risk of atrial fibrillation in older adults.}, journal = {Heart}, volume = {101}, year = {2015}, month = {2015 Sep}, pages = {1368-74}, abstract = {

BACKGROUND: Adiponectin has cardioprotective properties, suggesting that lower levels seen in obesity and diabetes could heighten risk of atrial fibrillation (AF). Among older adults, however, higher adiponectin has been linked to greater incidence of adverse outcomes associated with AF, although recent reports have shown this association to be U-shaped. We postulated that higher adiponectin would be linked to increased risk for AF in older adults in a U-shaped manner.

METHODS: We examined the associations of total and high-molecular-weight (HMW) adiponectin with incident AF among individuals free of prevalent cardiovascular disease (CVD) participating in a population-based cohort study of older adults (n=3190; age=74{\textpm}5 years).

RESULTS: During median follow-up of 11.4 years, there were 886 incident AF events. Adjusted cubic splines showed a positive and linear association between adiponectin and incident AF. After adjusting for potential confounders, including amino-terminal pro-B-type natriuretic peptide 1-76, the HR (95\% CI) for AF per SD increase in total adiponectin was 1.14 (1.05 to 1.24), while that for HMW adiponectin was 1.17 (1.08 to 1.27). Additional adjustment for putative mediators, including subclinical CVD, diabetes, lipids and inflammation, did not significantly affect these estimates.

CONCLUSIONS: The present findings demonstrate that higher, not lower, levels of adiponectin are independently associated with increased risk of AF in older adults despite its documented cardiometabolic benefits. Additional work is necessary to determine if adiponectin is a marker of failed counter-regulatory pathways or whether this hormone is directly harmful in the setting of or as a result of advanced age.

}, keywords = {Adiponectin, Age Factors, Aged, Aged, 80 and over, Aging, Atrial Fibrillation, Biomarkers, Female, Humans, Incidence, Linear Models, Male, Multivariate Analysis, Natriuretic Peptide, Brain, Peptide Fragments, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1468-201X}, doi = {10.1136/heartjnl-2014-307015}, author = {Macheret, Fima and Bartz, Traci M and Djouss{\'e}, Luc and Ix, Joachim H and Mukamal, Kenneth J and Zieman, Susan J and Siscovick, David S and Tracy, Russell P and Heckbert, Susan R and Psaty, Bruce M and Kizer, Jorge R} } @article {6808, title = {Intermediate and long-term risk of new-onset heart failure after hospitalization for pneumonia in elderly adults.}, journal = {Am Heart J}, volume = {170}, year = {2015}, month = {2015 Aug}, pages = {306-12}, abstract = {

BACKGROUND: Pneumonia is associated with high risk of heart failure (HF) in the short term (30 days) postinfection. Whether this association persists beyond this period is unknown.

METHODS: We studied 5,613 elderly (>=65 years) adults enrolled in the Cardiovascular Health Study between 1989 and 1994 at 4 US communities. Participants had no clinical diagnosis of HF at enrollment, and they were followed up through December 2010. Hospitalizations for pneumonia were identified using validated International Classification of Disease Ninth Revision codes. A centralized committee adjudicated new-onset HF events. Using Cox regression, we estimated adjusted hazard ratios (HRs) of new-onset HF at different time intervals after hospitalization for pneumonia.

RESULTS: A total of 652 participants hospitalized for pneumonia during follow-up were still alive and free of clinical diagnosis of HF by day 30 posthospitalization. Relative to the time of their hospitalization, new-onset HF occurred in 22 cases between 31 and 90 days (HR 6.9, 95\% CI 4.46-10.63, P < .001), 14 cases between 91 days and 6 months (HR 3.2, 95\% CI 1.88-5.50, P < .001), 20 cases between 6 months and 1 year (HR 2.6, 95\% CI 1.64-4.04, P < .001), 76 cases between 1 and 5 years (HR 1.7, 95\% CI 1.30-2.12, P < .001), and 71 cases after 5 years (HR 2.0, 95\% CI 1.56-2.58, P < .001). Results were robust to sensitivity analyses using stringent definitions of pneumonia and extreme assumptions for potential informative censoring.

CONCLUSION: Hospitalization for pneumonia is associated with increased risk of new-onset HF in the intermediate and long term. Studies should characterize the mechanisms of this association in order to prevent HF in elderly pneumonia survivors.

}, keywords = {Aged, Disease Progression, Female, Follow-Up Studies, Forecasting, Heart Failure, Hospitalization, Humans, Incidence, Inpatients, Male, Patient Readmission, Pneumonia, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors}, issn = {1097-6744}, doi = {10.1016/j.ahj.2015.04.028}, author = {Corrales-Medina, Vicente F and Taljaard, Monica and Yende, Sachin and Kronmal, Richard and Dwivedi, Girish and Newman, Anne B and Elkind, Mitchell S V and Lyles, Mary F and Chirinos, Julio A} } @article {6797, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {591-601}, abstract = {

BACKGROUND: Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).

STUDY DESIGN: Collaborative meta-analysis.

SETTING \& POPULATION: 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).

SELECTION CRITERIA FOR STUDIES: Available eGFR, ACR, and 50 or more AKI events.

PREDICTORS: Age, sex, race, eGFR, urine ACR, and interactions.

OUTCOME: Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

RESULTS: 16,480 (1.3\%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6\%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95\% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95\% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.

LIMITATIONS: Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.

CONCLUSIONS: Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

}, keywords = {Acute Kidney Injury, Adolescent, Adult, African Americans, Age Distribution, Aged, Albuminuria, Continental Population Groups, European Continental Ancestry Group, Female, Glomerular Filtration Rate, Humans, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Severity of Illness Index, Sex Distribution, Young Adult}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.337}, author = {Grams, Morgan E and Sang, Yingying and Ballew, Shoshana H and Gansevoort, Ron T and Kimm, Heejin and Kovesdy, Csaba P and Naimark, David and Oien, Cecilia and Smith, David H and Coresh, Josef and Sarnak, Mark J and Stengel, B{\'e}n{\'e}dicte and Tonelli, Marcello} } @article {6796, title = {A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.}, journal = {Am J Kidney Dis}, volume = {66}, year = {2015}, month = {2015 Oct}, pages = {602-12}, abstract = {

BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.

STUDY DESIGN: Meta-analysis of cohort studies.

SETTING \& POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.

SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.

PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.

OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.

RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.

LIMITATIONS: AKI identified by diagnostic code.

CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.

}, keywords = {Acute Kidney Injury, Adult, Aged, Comorbidity, Diabetes Mellitus, Disease Progression, Female, Glomerular Filtration Rate, Humans, Hypertension, Incidence, Kidney Failure, Chronic, Male, Middle Aged, Prognosis, Renal Insufficiency, Chronic}, issn = {1523-6838}, doi = {10.1053/j.ajkd.2015.02.338}, author = {James, Matthew T and Grams, Morgan E and Woodward, Mark and Elley, C Raina and Green, Jamie A and Wheeler, David C and de Jong, Paul and Gansevoort, Ron T and Levey, Andrew S and Warnock, David G and Sarnak, Mark J} } @article {6661, title = {NT-proBNP and troponin T and risk of rapid kidney function decline and incident CKD in elderly adults.}, journal = {Clin J Am Soc Nephrol}, volume = {10}, year = {2015}, month = {2015 Feb 6}, pages = {205-14}, abstract = {

BACKGROUND AND OBJECTIVES: Elevations in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T are associated with poor cardiovascular outcomes. Whether elevations in these cardiac biomarkers are associated with decline in kidney function was evaluated.

DESIGN, SETTING, PARTICIPANTS, \& MEASUREMENTS: N-terminal pro-B-type natriuretic peptide and troponin T were measured at baseline in 3752 participants free of heart failure in the Cardiovascular Health Study. eGFR was determined from the Chronic Kidney Disease Epidemiology Collaboration equation using serum cystatin C. Rapid decline in kidney function was defined as decline in serum cystatin C eGFR>=30\%, and incident CKD was defined as the onset of serum cystatin C eGFR<60 among those without CKD at baseline (n=2786). Cox regression models were used to examine the associations of each biomarker with kidney function decline adjusting for demographics, baseline serum cystatin C eGFR, diabetes, and other CKD risk factors.

RESULTS: In total, 503 participants had rapid decline in serum cystatin C eGFR over a mean follow-up time of 6.41 (1.81) years, and 685 participants developed incident CKD over a mean follow-up time of 6.41 (1.74) years. Participants in the highest quartile of N-terminal pro-B-type natriuretic peptide (>237 pg/ml) had an 67\% higher risk of rapid decline and 38\% higher adjusted risk of incident CKD compared with participants in the lowest quartile (adjusted hazard ratio for serum cystatin C eGFR rapid decline, 1.67; 95\% confidence interval, 1.25 to 2.23; hazard ratio for incident CKD, 1.38; 95\% confidence interval, 1.08 to 1.76). Participants in the highest category of troponin T (>10.58 pg/ml) had 80\% greater risk of rapid decline compared with participants in the lowest category (adjusted hazard ratio, 1.80; 95\% confidence interval, 1.35 to 2.40). The association of troponin T with incident CKD was not statistically significant (hazard ratio, 1.17; 95\% confidence interval, 0.92 to 1.50).

CONCLUSIONS: Elevated N-terminal pro-B-type natriuretic peptide and troponin T are associated with rapid decline of kidney function and incident CKD. Additional studies are needed to evaluate the mechanisms that may explain this association.

}, keywords = {Age Factors, Aged, Aging, Biomarkers, Cystatin C, Disease Progression, Female, Glomerular Filtration Rate, Humans, Incidence, Kidney, Linear Models, Longitudinal Studies, Male, Natriuretic Peptide, Brain, Peptide Fragments, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prospective Studies, Renal Insufficiency, Chronic, Risk Factors, Time Factors, Troponin T, United States, Up-Regulation}, issn = {1555-905X}, doi = {10.2215/CJN.04910514}, author = {Bansal, Nisha and Katz, Ronit and Dalrymple, Lorien and de Boer, Ian and DeFilippi, Christopher and Kestenbaum, Bryan and Park, Meyeon and Sarnak, Mark and Seliger, Stephen and Shlipak, Michael} } @article {6809, title = {Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {35}, year = {2015}, month = {2015 Oct}, pages = {2246-53}, abstract = {

OBJECTIVE: Interleukin (IL) -2 receptor subunit α regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα (sIL-2Rα) and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic determinants of sIL-2Rα levels.

APPROACH AND RESULTS: We measured baseline levels of sIL-2Rα in 4408 European American (EA) and 766 African American (AA) adults from the Cardiovascular Health Study (CHS) and examined associations with baseline CVD risk factors, subclinical CVD, and incident CVD events. We also performed a genome-wide association study for sIL-2Rα in CHS (2964 EAs and 683 AAs) and further combined CHS EA results with those from two other EA cohorts in a meta-analysis (n=4464 EAs). In age, sex- and race- adjusted models, sIL-2Rα was positively associated with current smoking, type 2 diabetes mellitus, hypertension, insulin, waist circumference, C-reactive protein, IL-6, fibrinogen, internal carotid wall thickness, all-cause mortality, CVD mortality, and incident CVD, stroke, and heart failure. When adjusted for baseline CVD risk factors and subclinical CVD, associations with all-cause mortality, CVD mortality, and heart failure remained significant in both EAs and AAs. In the EA genome-wide association study analysis, we observed 52 single-nucleotide polymorphisms in the chromosome 10p15-14 region, which contains IL2RA, IL15RA, and RMB17, that reached genome-wide significance (P<5{\texttimes}10(-8)). The most significant single-nucleotide polymorphism was rs7911500 (P=1.31{\texttimes}10(-75)). The EA meta-analysis results were highly consistent with CHS-only results. No single-nucleotide polymorphisms reached statistical significance in the AAs.

CONCLUSIONS: These results support a role for sIL-2Rα in atherosclerosis and provide evidence for multiple-associated single-nucleotide polymorphisms at chromosome 10p15-14.

}, keywords = {Adult, African Americans, Age Distribution, Aged, Cardiovascular Diseases, Cohort Studies, Coronary Artery Disease, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Incidence, Interleukin-2 Receptor alpha Subunit, Kaplan-Meier Estimate, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Assessment, Sex Distribution, Survival Analysis}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.305289}, author = {Durda, Peter and Sabourin, Jeremy and Lange, Ethan M and Nalls, Mike A and Mychaleckyj, Josyf C and Jenny, Nancy Swords and Li, Jin and Walston, Jeremy and Harris, Tamara B and Psaty, Bruce M and Valdar, William and Liu, Yongmei and Cushman, Mary and Reiner, Alex P and Tracy, Russell P and Lange, Leslie A} } @article {6663, title = {Plasma phospholipid very-long-chain saturated fatty acids and incident diabetes in older adults: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {101}, year = {2015}, month = {2015 May}, pages = {1047-54}, abstract = {

BACKGROUND: Circulating saturated fatty acids (SFAs) are integrated biomarkers of diet and metabolism that may influence the pathogenesis of diabetes. In epidemiologic studies, circulating levels of palmitic acid (16:0) are associated with diabetes; however, very-long-chain SFAs (VLSFAs), with 20 or more carbons, differ from palmitic acid in their biological activities, and little is known of the association of circulating VLSFA with diabetes.

OBJECTIVE: By using data from the Cardiovascular Health Study, we examined the associations of plasma phospholipid VLSFA levels measured at baseline with subsequent incident diabetes.

DESIGN: A total of 3179 older adults, with a mean age of 75 y at study baseline (1992-1993), were followed through 2011. We used multiple proportional hazards regression to examine the associations of arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0) with diabetes.

RESULTS: Baseline levels of each VLSFA were cross-sectionally associated with lower triglyceride levels and lower circulating palmitic acid. We identified 284 incident diabetes cases during follow-up. Compared with the lowest quartile, levels of arachidic acid in the highest quartile of the fatty acid distribution were associated with a 47\% lower risk of diabetes (95\% CI: 23\%, 63\%; P-trend: <0.001), after adjustment for demographics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of behenic and lignoceric acid were similarly associated with 33\% (95\% CI: 6\%, 53\%; P-trend: 0.02) and 37\% (95\% CI: 11\%, 55\%; P-trend: 0.01) lower diabetes risk, respectively. Adjustment for triglycerides and palmitic acid attenuated the associations toward the null, and only the association of arachidic acid remained statistically significant (32\% lower risk for fourth vs. first quartile; P-trend: 0.04).

CONCLUSIONS: These results suggest that circulating VLSFAs are associated with a lower risk of diabetes, and these associations may be mediated by lower triglycerides and palmitic acid. The study highlights the need to distinguish the effects of different SFAs and to explore determinants of circulating VLSFAs. This trial was registered at clinicaltrials.gov as NCT00005133.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Cross-Sectional Studies, Diabetes Mellitus, Diet, Eicosanoic Acids, Fatty Acids, Fatty Acids, Nonesterified, Female, Follow-Up Studies, Humans, Incidence, Male, Observational Studies as Topic, Palmitic Acid, Phospholipids, Prospective Studies, Risk Factors, Triglycerides}, issn = {1938-3207}, doi = {10.3945/ajcn.114.101857}, author = {Lemaitre, Rozenn N and Fretts, Amanda M and Sitlani, Colleen M and Biggs, Mary L and Mukamal, Kenneth and King, Irena B and Song, Xiaoling and Djouss{\'e}, Luc and Siscovick, David S and McKnight, Barbara and Sotoodehnia, Nona and Kizer, Jorge R and Mozaffarian, Dariush} } @article {6616, title = {Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study.}, journal = {Am J Clin Nutr}, volume = {101}, year = {2015}, month = {2015 Jan}, pages = {153-63}, abstract = {

BACKGROUND: Experimental evidence suggests that hepatic de novo lipogenesis (DNL) affects insulin homeostasis via synthesis of saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs). Few prospective studies have used fatty acid biomarkers to assess associations with type 2 diabetes.

OBJECTIVES: We investigated associations of major circulating SFAs [palmitic acid (16:0) and stearic acid (18:0)] and MUFA [oleic acid (18:1n-9)] in the DNL pathway with metabolic risk factors and incident diabetes in community-based older U.S. adults in the Cardiovascular Health Study. We secondarily assessed other DNL fatty acid biomarkers [myristic acid (14:0), palmitoleic acid (16:1n-7), 7-hexadecenoic acid (16:1n-9), and vaccenic acid (18:1n-7)] and estimated dietary SFAs and MUFAs.

DESIGN: In 3004 participants free of diabetes, plasma phospholipid fatty acids were measured in 1992, and incident diabetes was identified by medication use and blood glucose. Usual diets were assessed by using repeated food-frequency questionnaires. Multivariable linear and Cox regression were used to assess associations with metabolic risk factors and incident diabetes, respectively.

RESULTS: At baseline, circulating palmitic acid and stearic acid were positively associated with adiposity, triglycerides, inflammation biomarkers, and insulin resistance (P-trend < 0.01 each), whereas oleic acid showed generally beneficial associations (P-trend < 0.001 each). During 30,763 person-years, 297 incident diabetes cases occurred. With adjustment for demographics and lifestyle, palmitic acid (extreme-quintile HR: 1.89; 95\% CI: 1.27, 2.83; P-trend = 0.001) and stearic acid (HR: 1.62; 95\% CI: 1.09, 2.41; P-trend = 0.006) were associated with higher diabetes risk, whereas oleic acid was not significantly associated. In secondary analyses, vaccenic acid was inversely associated with diabetes (HR: 0.56; 95\% CI: 0.38, 0.83; P-trend = 0.005). Other fatty acid biomarkers and estimated dietary SFAs or MUFAs were not significantly associated with incident diabetes.

CONCLUSIONS: In this large prospective cohort, circulating palmitic acid and stearic acid were associated with higher diabetes risk, and vaccenic acid was associated with lower diabetes risk. These results indicate a need for additional investigation of biological mechanisms linking specific fatty acids in the DNL pathway to the pathogenesis of diabetes.

}, keywords = {Aged, Biomarkers, Cohort Studies, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Humans, Incidence, Lipogenesis, Liver, Male, Palmitic Acid, Phospholipids, Prevalence, Proportional Hazards Models, Risk Factors, Stearic Acids, United States, Up-Regulation}, issn = {1938-3207}, doi = {10.3945/ajcn.114.092601}, author = {Ma, Wenjie and Wu, Jason H Y and Wang, Qianyi and Lemaitre, Rozenn N and Mukamal, Kenneth J and Djouss{\'e}, Luc and King, Irena B and Song, Xiaoling and Biggs, Mary L and Delaney, Joseph A and Kizer, Jorge R and Siscovick, David S and Mozaffarian, Dariush} } @article {6930, title = {Prospective study of circulating factor XI and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Am J Hematol}, volume = {90}, year = {2015}, month = {2015 Nov}, pages = {1047-51}, abstract = {

Elevated plasma concentrations of coagulation factor XI may increase risk of venous thromboembolism (VTE), but prospective data are limited. We studied prospectively the associations of plasma factor XI and a key F11 genetic variant with incident VTE in whites and African-Americans. We measured factor XI in 16,299 participants, initially free of VTE, in two prospective population cohorts. We also measured the F11 single nucleotide polymorphism rs4241824, which a genome-wide association study had linked to factor XI concentration. During follow-up, we identified 606 VTEs. The age, race, sex, and study-adjusted hazard ratio of VTE increased across factor XI quintiles (P < 0.001 for trend), and the hazard ratio was 1.51 (95\% CI 1.16, 1.97) for the highest versus lowest quintile overall, and was 1.42 (95\% CI 1.03, 1.95) in whites and 1.72 (95\% CI 1.08, 2.73) in African-Americans. In whites, the F11 variant was associated with both factor XI concentration and VTE incidence (1.15-fold greater incidence of VTE per risk allele). In African-Americans, these associations were absent. In conclusion, this cohort study documented that an elevated plasma factor XI concentration is a risk factor for VTE over extended follow-up, not only in whites but also in African-Americans. In whites, the association of the F11 genetic variant with VTE suggests a causal relation, but we did not observe this genetic relation in African-Americans.

}, keywords = {African Americans, Aged, Alleles, European Continental Ancestry Group, Factor XI, Female, Gene Expression, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Polymorphism, Single Nucleotide, Proportional Hazards Models, Prospective Studies, Risk Factors, United States, Venous Thromboembolism}, issn = {1096-8652}, doi = {10.1002/ajh.24168}, author = {Folsom, Aaron R and Tang, Weihong and Roetker, Nicholas S and Heckbert, Susan R and Cushman, Mary and Pankow, James S} } @article {6876, title = {Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.}, journal = {PLoS One}, volume = {10}, year = {2015}, month = {2015}, pages = {e0132321}, abstract = {

BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events.

METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity.

RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites.

CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

}, keywords = {Adult, Age Distribution, Aged, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, HDL, Cholesterol, LDL, Comorbidity, Continental Population Groups, Diabetes Mellitus, Dyslipidemias, Ethnic Groups, Female, Follow-Up Studies, Global Health, Humans, Hypertension, Incidence, Linear Models, Male, Middle Aged, Myocardial Infarction, Prevalence, Proportional Hazards Models, Risk Factors, Smoking, Stroke}, issn = {1932-6203}, doi = {10.1371/journal.pone.0132321}, author = {Gijsberts, Crystel M and Groenewegen, Karlijn A and Hoefer, Imo E and Eijkemans, Marinus J C and Asselbergs, Folkert W and Anderson, Todd J and Britton, Annie R and Dekker, Jacqueline M and Engstr{\"o}m, Gunnar and Evans, Greg W and de Graaf, Jacqueline and Grobbee, Diederick E and Hedblad, Bo and Holewijn, Suzanne and Ikeda, Ai and Kitagawa, Kazuo and Kitamura, Akihiko and de Kleijn, Dominique P V and Lonn, Eva M and Lorenz, Matthias W and Mathiesen, Ellisiv B and Nijpels, Giel and Okazaki, Shuhei and O{\textquoteright}Leary, Daniel H and Pasterkamp, Gerard and Peters, Sanne A E and Polak, Joseph F and Price, Jacqueline F and Robertson, Christine and Rembold, Christopher M and Rosvall, Maria and Rundek, Tatjana and Salonen, Jukka T and Sitzer, Matthias and Stehouwer, Coen D A and Bots, Michiel L and den Ruijter, Hester M} } @article {6771, title = {Resting heart rate and risk of incident heart failure: three prospective cohort studies and a systematic meta-analysis.}, journal = {J Am Heart Assoc}, volume = {4}, year = {2015}, month = {2015 Jan}, pages = {e001364}, abstract = {

BACKGROUND: The relationship between resting heart rate (RHR) and incident heart failure (HF) has been questioned.

METHODS AND RESULTS: RHR was assessed at baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded 1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm) versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95\% confidence interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95\% CI 1.10 to 1.53) with further adjustment for body mass index, history of diabetes, hypertension, smoking status, serum creatinine, and left ventricular hypertrophy. These findings remained consistent in analyses accounting for incident coronary heart disease, excluding individuals with prior cardiovascular events, or those taking beta-blockers; and in subgroups defined by several individual participant characteristics. In a pooled random effects meta-analysis of 7 population-based studies (43 051 participants and 3476 HF events), the overall hazard ratio comparing top versus bottom fourth of RHR was 1.40 (95\% CI: 1.19 to 1.64).

CONCLUSIONS: There is a non-linear association between RHR and incident HF. Further research is needed to understand the physiologic foundations of this association.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Aging, Cohort Studies, Female, Heart Failure, Heart Rate, Humans, Incidence, Japan, Male, Predictive Value of Tests, Prospective Studies, Rest, Risk Assessment, Severity of Illness Index, Sex Distribution, Survival Rate}, issn = {2047-9980}, doi = {10.1161/JAHA.114.001364}, author = {Khan, Hassan and Kunutsor, Setor and Kalogeropoulos, Andreas P and Georgiopoulou, Vasiliki V and Newman, Anne B and Harris, Tamara B and Bibbins-Domingo, Kirsten and Kauhanen, Jussi and Gheorghiade, Mihai and Fonarow, Gregg C and Kritchevsky, Stephen B and Laukkanen, Jari A and Butler, Javed} } @article {6702, title = {Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.}, journal = {Heart Rhythm}, volume = {12}, year = {2015}, month = {2015 May}, pages = {879-85}, abstract = {

BACKGROUND: Various mechanisms in cardiac remodeling related to atrial fibrillation (AF) lead to elevated circulating cardiac troponin levels, but little is known about such elevations upstream to AF onset.

OBJECTIVE: The purpose of this study was to study the association between circulating troponin levels as assessed by a highly sensitive cardiac troponin T (hs-cTnT) assay and incident atrial fibrillation (AF).

METHODS: In a large prospective cohort of ambulatory older adults [the Cardiovascular Health Study (CHS)], hs-cTnT levels were measured in sera that were collected at enrollment from 4262 participants without AF (2871 with follow-up measurements). Incident AF was identified by electrocardiograms during CHS visits, hospital discharge diagnoses, and Medicare files, including outpatient and physician claims diagnoses.

RESULTS: Over median follow-up of 11.2 years (interquartile range 6.1-16.5), 1363 participants (32.0\%) developed AF. Higher baseline levels of hs-cTnT were associated with incident AF in covariate-adjusted analyses accounting for demographics, traditional risk factors, and incident heart failure in time-dependent analyzes (hazard ratio for 3rd tertile vs undetectable 1.75, 95\% confidence interval 1.48-2.08). This association was statistically significant in analyses that additionally adjusted for biomarkers of inflammation and hemodynamic strain (hazard ratio for 3rd tertile vs undetectable 1.38, 95\% confidence interval 1.16-1.65). Significant associations were also found when hs-cTnT levels were treated as a continuous variable and when examining change from baseline of hs-cTnT levels and incident AF.

CONCLUSION: The findings show a significant association of circulating troponin levels in ambulatory older adults with incident AF beyond that of traditional risk factors, incident heart failure, and biomarkers of inflammation and hemodynamic strain.

}, keywords = {Aged, Atrial Fibrillation, Biomarkers, Electrocardiography, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Outpatients, Risk Assessment, Risk Factors, Statistics as Topic, Troponin T, United States}, issn = {1556-3871}, doi = {10.1016/j.hrthm.2015.01.020}, author = {Hussein, Ayman A and Bartz, Traci M and Gottdiener, John S and Sotoodehnia, Nona and Heckbert, Susan R and Lloyd-Jones, Donald and Kizer, Jorge R and Christenson, Robert and Wazni, Oussama and DeFilippi, Christopher} } @article {6854, title = {Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study.}, journal = {Diabetes Care}, volume = {38}, year = {2015}, month = {2015 Nov}, pages = {2050-8}, abstract = {

OBJECTIVE: We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults.

RESEARCH DESIGN AND METHODS: Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants >=65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 1989-1994. In 1989-1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989-1990 and again in 1992-1993, 1994-1995, 1996-1997, and 1998-1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history.

RESULTS: Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95\% CI 1.19-2.86]), snoring (HR 1.27 [95\% CI 0.95-1.71]), and daytime sleepiness (HR 1.54 [95\% CI 1.13-2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes.

CONCLUSIONS: Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may prove useful in identifying candidates for lifestyle or pharmacological therapy. Further studies are needed to determine whether insomnia symptoms affect the risk of diabetes in younger adults.

}, keywords = {Adult, Aged, Blood Glucose, Cardiovascular System, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Fasting, Female, Glucose Tolerance Test, Humans, Incidence, Insulin, Insulin Resistance, Male, Middle Aged, Sleep Apnea Syndromes, Sleep Initiation and Maintenance Disorders, Snoring, United States}, issn = {1935-5548}, doi = {10.2337/dc15-0137}, author = {Strand, Linn Beate and Carnethon, Mercedes and Biggs, Mary Lou and Djouss{\'e}, Luc and Kaplan, Robert C and Siscovick, David S and Robbins, John A and Redline, Susan and Patel, Sanjay R and Janszky, Imre and Mukamal, Kenneth J} } @article {6800, title = {Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis.}, journal = {J Clin Endocrinol Metab}, volume = {100}, year = {2015}, month = {2015 Jun}, pages = {2181-91}, abstract = {

OBJECTIVE: The objective was to determine the risk of stroke associated with subclinical hypothyroidism.

DATA SOURCES AND STUDY SELECTION: Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data on thyroid function and stroke outcome. Euthyroidism was defined as TSH levels of 0.45-4.49 mIU/L, and subclinical hypothyroidism was defined as TSH levels of 4.5-19.9 mIU/L with normal T4 levels.

DATA EXTRACTION AND SYNTHESIS: We collected individual participant data on 47 573 adults (3451 subclinical hypothyroidism) from 17 cohorts and followed up from 1972-2014 (489 192 person-years). Age- and sex-adjusted pooled hazard ratios (HRs) for participants with subclinical hypothyroidism compared to euthyroidism were 1.05 (95\% confidence interval [CI], 0.91-1.21) for stroke events (combined fatal and nonfatal stroke) and 1.07 (95\% CI, 0.80-1.42) for fatal stroke. Stratified by age, the HR for stroke events was 3.32 (95\% CI, 1.25-8.80) for individuals aged 18-49 years. There was an increased risk of fatal stroke in the age groups 18-49 and 50-64 years, with a HR of 4.22 (95\% CI, 1.08-16.55) and 2.86 (95\% CI, 1.31-6.26), respectively (p trend 0.04). We found no increased risk for those 65-79 years old (HR, 1.00; 95\% CI, 0.86-1.18) or >= 80 years old (HR, 1.31; 95\% CI, 0.79-2.18). There was a pattern of increased risk of fatal stroke with higher TSH concentrations.

CONCLUSIONS: Although no overall effect of subclinical hypothyroidism on stroke could be demonstrated, an increased risk in subjects younger than 65 years and those with higher TSH concentrations was observed.

}, keywords = {Adult, Asymptomatic Diseases, Female, Humans, Hypothyroidism, Incidence, Male, Risk Factors, Stroke, Thyrotropin}, issn = {1945-7197}, doi = {10.1210/jc.2015-1438}, author = {Chaker, Layal and Baumgartner, Christine and den Elzen, Wendy P J and Ikram, M Arfan and Blum, Manuel R and Collet, Tinh-Hai and Bakker, Stephan J L and Dehghan, Abbas and Drechsler, Christiane and Luben, Robert N and Hofman, Albert and Portegies, Marileen L P and Medici, Marco and Iervasi, Giorgio and Stott, David J and Ford, Ian and Bremner, Alexandra and Wanner, Christoph and Ferrucci, Luigi and Newman, Anne B and Dullaart, Robin P and Sgarbi, Jos{\'e} A and Ceresini, Graziano and Maciel, Rui M B and Westendorp, Rudi G and Jukema, J Wouter and Imaizumi, Misa and Franklyn, Jayne A and Bauer, Douglas C and Walsh, John P and Razvi, Salman and Khaw, Kay-Tee and Cappola, Anne R and V{\"o}lzke, Henry and Franco, Oscar H and Gussekloo, Jacobijn and Rodondi, Nicolas and Peeters, Robin P} } @article {6551, title = {Thyroid function in the euthyroid range and adverse outcomes in older adults.}, journal = {J Clin Endocrinol Metab}, volume = {100}, year = {2015}, month = {2015 Mar}, pages = {1088-96}, abstract = {

CONTEXT: The appropriateness of current reference ranges for thyroid function testing in older adults has been questioned.

OBJECTIVE: This study aimed to determine the relationship between thyroid function tests within the euthyroid range and adverse outcomes in older adults not taking thyroid medication.

DESIGN, SETTING, AND PARTICIPANTS: US community-dwelling adults years of older (n = 2843) enrolled onto the Cardiovascular Health Study with TSH, free T4 (FT4), and total T3 concentrations in the euthyroid range.

MAIN OUTCOME MEASURES: Incidence of atrial fibrillation, coronary heart disease, heart failure, hip fracture, dementia, and all-cause death were measured.

RESULTS: No departures from linearity were detected. Higher TSH was negatively associated (P = .03) and higher FT4 was positively associated (P = .007) with mortality. Higher FT4 was associated with atrial fibrillation (P < .001) and heart failure (P = .004). Compared with the first quartile, individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia (P < .05) and those with FT4 in the fourth quartile had higher incidences of atrial fibrillation, coronary heart disease, heart failure, and mortality (11.0, 8.0, 7.8, and 14.3 per 1000 person-years, respectively, all P < .05). Total T3 was not associated with any outcome.

CONCLUSIONS: Higher TSH and lower FT4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events in older people, including mortality. This suggests tolerance for lower thyroid hormone levels in this age group. Clinical trials are needed to evaluate the risk-benefit profile of new thresholds for initiating treatment and optimal target concentrations for thyroid hormone replacement in older people.

}, keywords = {Aged, Aged, 80 and over, Aging, Atrial Fibrillation, Cause of Death, Coronary Disease, Dementia, Female, Heart Failure, Hip Fractures, Humans, Incidence, Male, Prognosis, Reference Values, Survival Analysis, Thyroid Function Tests, Thyroid Gland}, issn = {1945-7197}, doi = {10.1210/jc.2014-3586}, author = {Cappola, Anne R and Arnold, Alice M and Wulczyn, Kendra and Carlson, Michelle and Robbins, John and Psaty, Bruce M} } @article {6770, title = {Urinary uromodulin, kidney function, and cardiovascular disease in elderly adults.}, journal = {Kidney Int}, volume = {88}, year = {2015}, month = {2015 Nov}, pages = {1126-34}, abstract = {

Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30\% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23\% lower odds of eGFR decline (odds ratio 0.77 (95\% CI 0.62-0.96)) and a 10\% lower risk of mortality (hazard ratio 0.90 (95\% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.

}, keywords = {Aged, Aged, 80 and over, Albuminuria, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Creatinine, Disease Progression, Female, Glomerular Filtration Rate, Heart Failure, Humans, Incidence, Kidney Failure, Chronic, Male, Proportional Hazards Models, Uromodulin}, issn = {1523-1755}, doi = {10.1038/ki.2015.192}, author = {Garimella, Pranav S and Biggs, Mary L and Katz, Ronit and Ix, Joachim H and Bennett, Michael R and Devarajan, Prasad and Kestenbaum, Bryan R and Siscovick, David S and Jensen, Majken K and Shlipak, Michael G and Chaves, Paulo H M and Sarnak, Mark J} } @article {6561, title = {Variation in resting heart rate over 4 years and the risks of myocardial infarction and death among older adults.}, journal = {Heart}, volume = {101}, year = {2015}, month = {2015 Jan}, pages = {132-8}, abstract = {

OBJECTIVE: Resting heart rate (RHR) is an established predictor of myocardial infarction (MI) and mortality, but the relationship between variation in RHR over a period of several years and health outcomes is unclear. We evaluated the relationship between long-term variation in RHR and the risks of incident MI and mortality among older adults.

METHODS: 1991 subjects without cardiovascular disease from the Cardiovascular Health Study were included. RHR was taken from resting ECGs at the first five annual study visits. RHR mean, trend and variation were estimated with linear regression. Subjects were followed for incident MI and death until December 2010. HRs for RHR mean, trend and variation are reported for differences of 10 bpm, 2 bpm/year and 2 bpm, respectively.

RESULTS: 262 subjects had an incident MI event (13\%) and 1326 died (67\%) during 12 years of median follow-up. In primary analyses adjusted for cardiovascular risk factors, RHR mean (HR 1.12; 95\% CI 1.05 to 1.20) and variation (HR 1.08; 95\% CI 1.03 to 1.13) were associated with the risk of death while trend was not. None of the RHR variables were significantly associated with the risk of incident MI events; however, CIs were wide and the MI associations with RHR variables were not significantly different from the mortality associations. Adjusting for additional variables did not affect estimates, and there were no significant interactions with sex.

CONCLUSIONS: Variation in RHR over a period of several years represents a potential predictor of long-term mortality among older persons free of cardiovascular disease.

}, keywords = {Aged, Aged, 80 and over, Cause of Death, Electrocardiography, Female, Follow-Up Studies, Heart Rate, Humans, Incidence, Linear Models, Male, Myocardial Infarction, Outcome Assessment (Health Care), Prognosis, Proportional Hazards Models, Prospective Studies, Rest, Risk Factors, Time, Washington}, issn = {1468-201X}, doi = {10.1136/heartjnl-2014-306046}, author = {Floyd, James S and Sitlani, Colleen M and Wiggins, Kerri L and Wallace, Erin and Suchy-Dicey, Astrid and Abbasi, Siddique A and Carnethon, Mercedes R and Siscovick, David S and Sotoodehnia, Nona and Heckbert, Susan R and McKnight, Barbara and Rice, Kenneth M and Psaty, Bruce M} } @article {6773, title = {Voxel Level Survival Analysis of Grey Matter Volume and Incident Mild Cognitive Impairment or Alzheimer{\textquoteright}s Disease.}, journal = {J Alzheimers Dis}, volume = {46}, year = {2015}, month = {2015}, pages = {167-78}, abstract = {

The purpose of this study was to identify, at the voxel level, brain regions associated with the time to develop mild cognitive impairment (MCI) or Alzheimer{\textquoteright}s disease (AD) from normal cognition. We analyzed incident MCI (n = 58) or AD (n = 151) in 292 cognitively normal participants in the Cardiovascular Health Study-Cognition Study (mean age = 79.2 {\textpm} 3.6 years). We used segmented, modulated grey matter maps from 3D (spoiled gradient echo) MRI scans obtained in 1998/99 (with clinical follow-up through 2012) that were smoothed with a 3-D 4 mm Gaussian filter. We fit approximately 1.92 million voxel-level Cox proportional hazard models to examine the grey matter volume effect on time to event, adjusting for age, sex, and diabetes. We used the significance threshold of p <  0.005 with contiguity threshold of at least 68 voxels (false detection probability <2.5{\texttimes}10 -8). Areas within the mesial temporal lobe (MTL), anterior temporal lobe, hippocampus, and posterior cingulate gyrus were associated with time to MCI or AD. The presence of white matter lesions (a marker of small vessel disease in the brain) was associated with the volumes of the MTL and precuneus; MRI-identified infarcts also predicted MTL volume. These findings are important because we identified critical brain regions that predict a person{\textquoteright}s increased likelihood of developing MCI or AD over a decade prior to the onset of clinical symptoms; these critical brain regions were themselves affected by the presence of vascular disease.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Chi-Square Distribution, Disease Progression, Female, Gray Matter, Humans, Incidence, Magnetic Resonance Imaging, Male, Mild Cognitive Impairment, Neuropsychological Tests, Psychiatric Status Rating Scales, Survival Analysis}, issn = {1875-8908}, doi = {10.3233/JAD-150047}, author = {Zeifman, Lubov E and Eddy, William F and Lopez, Oscar L and Kuller, Lewis H and Raji, Cyrus and Thompson, Paul M and Becker, James T} } @article {6931, title = {APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Feb}, pages = {398-403}, abstract = {

OBJECTIVE: We sought to evaluate the cardiovascular impact of coding variants in the apolipoprotein L1 gene APOL1 that protect against trypanosome infection but have been associated with kidney disease among African Americans.

APPROACH AND RESULTS: As part of the Cardiovascular Health Study, a population-based cohort of Americans aged >=65 years, we genotyped APOL1 polymorphisms rs73885319 and rs71785153 and examined kidney function, subclinical atherosclerosis, and incident cardiovascular disease and death over 13 years of follow-up among 91 African Americans with 2 risk alleles, 707 other African Americans, and 4964 white participants. The high-risk genotype with 2 risk alleles was associated with 2-fold higher levels of albuminuria and lower ankle-brachial indices but similar carotid intima-media thickness among African Americans. Median survival among high-risk African Americans was 9.9 years (95\% confidence interval [CI], 8.7-11.9), compared with 13.6 years (95\% CI, 12.5-14.3) among other African Americans and 13.3 years (95\% CI, 13.0-13.6) among whites (P=0.03). The high-risk genotype was also associated with increased risk for incident myocardial infarction (adjusted hazard ratio 1.8; 95\% CI, 1.1-3.0) and mortality (adjusted hazard ratio 1.3; 95\% CI 1.0-1.7). Albuminuria and risk for myocardial infarction and mortality were nearly identical between African Americans with 0 to 1 risk alleles and whites.

CONCLUSIONS: APOL1 genotype is associated with albuminuria, subclinical atherosclerosis, incident myocardial infarction, and mortality in older African Americans. African Americans without 2 risk alleles do not differ significantly in risk of myocardial infarction or mortality from whites. APOL1 trypanolytic variants may account for a substantial proportion of the excess risk of chronic disease in African Americans.

}, keywords = {African Americans, Age Factors, Aged, Albuminuria, Apolipoproteins, Atherosclerosis, Cardiovascular Diseases, Cause of Death, European Continental Ancestry Group, Female, Gene Frequency, Genetic Predisposition to Disease, Health Status Disparities, Heterozygote, Homozygote, Humans, Incidence, Kaplan-Meier Estimate, Kidney Diseases, Lipoproteins, HDL, Male, Myocardial Infarction, Phenotype, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.305970}, author = {Mukamal, Kenneth J and Tremaglio, Joseph and Friedman, David J and Ix, Joachim H and Kuller, Lewis H and Tracy, Russell P and Pollak, Martin R} } @article {7002, title = {Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {64}, year = {2016}, month = {2016 Apr}, pages = {838-43}, abstract = {

OBJECTIVES: To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability.

DESIGN: Prospective cohort study.

SETTING: Cardiovascular Health Study.

PARTICIPANTS: Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded.

MEASUREMENTS: Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models.

RESULTS: Over an average of 7.0 years of follow-up, 660 individuals (16.3\%) developed incident AF, and 3,112 (77\%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95\% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95\% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure.

CONCLUSION: These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Atrial Fibrillation, Disability Evaluation, Electrocardiography, Female, Geriatric Assessment, Humans, Incidence, Longevity, Longitudinal Studies, Male, Medicare, Prevalence, Prospective Studies, Survival Rate, United States}, issn = {1532-5415}, doi = {10.1111/jgs.14037}, author = {Wallace, Erin R and Siscovick, David S and Sitlani, Colleen M and Dublin, Sascha and Mitchell, Pamela H and Odden, Michelle C and Hirsch, Calvin H and Thielke, Stephen and Heckbert, Susan R} } @article {6996, title = {Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {36}, year = {2016}, month = {2016 Apr}, pages = {750-6}, abstract = {

OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged >=65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C-reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95\% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95\% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp-PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95\% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95\% confidence interval 1.09, 1.50).

CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp-PLA2 reduces the incidence of PAD.

}, keywords = {1-Alkyl-2-acetylglycerophosphocholine Esterase, Age Factors, Aged, Aging, Ankle Brachial Index, Biomarkers, Chi-Square Distribution, Female, Humans, Incidence, Inflammation Mediators, Logistic Models, Male, Odds Ratio, Peripheral Arterial Disease, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Time Factors, United States, Up-Regulation}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.115.306647}, author = {Garg, Parveen K and Arnold, Alice M and Hinckley Stukovsky, Karen D and Koro, Carol and Jenny, Nancy S and Mukamal, Kenneth J and Criqui, Michael H and Furberg, Curt D and Newman, Anne B and Cushman, Mary} } @article {6850, title = {Relations of Postload and Fasting Glucose With Incident Cardiovascular Disease and Mortality Late in Life: The Cardiovascular Health Study.}, journal = {J Gerontol A Biol Sci Med Sci}, volume = {71}, year = {2016}, month = {2016 Mar}, pages = {370-7}, abstract = {

BACKGROUND: Older adults have a high prevalence of postload hyperglycemia. Postload glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in the oldest old are sparse.

METHODS: Fasting and 2-hour postload glucose were measured in community-dwelling older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD) and mortality using standard Cox regression and competing-risks analyses and assessed improvement in prediction-model discrimination with the c-statistic.

RESULTS: Among 2,394 participants without treated diabetes and available data on glycemic measures, there were 579 ASCVD events and 1,698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with both outcomes were abolished, but those for postload glucose were largely unchanged. Consistent findings were observed for ASCVD in competing-risks models.

CONCLUSION: In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life.

}, keywords = {Aged, Aging, Blood Glucose, Cardiovascular Diseases, Fasting, Female, Follow-Up Studies, Glucose, Glucose Tolerance Test, Health Surveys, Humans, Incidence, Male, Proportional Hazards Models, Prospective Studies, Risk Assessment, Risk Factors, Survival Rate, United States}, issn = {1758-535X}, doi = {10.1093/gerona/glv106}, author = {Brutsaert, Erika F and Shitole, Sanyog and Biggs, Mary Lou and Mukamal, Kenneth J and deBoer, Ian H and Thacker, Evan L and Barzilay, Joshua I and Djouss{\'e}, Luc and Ix, Joachim H and Smith, Nicholas L and Kaplan, Robert C and Siscovick, David S and Psaty, Bruce M and Kizer, Jorge R} } @article {6998, title = {Subclinical Cardiovascular Disease and Death, Dementia, and Coronary Heart Disease in Patients 80+ Years.}, journal = {J Am Coll Cardiol}, volume = {67}, year = {2016}, month = {2016 Mar 8}, pages = {1013-22}, abstract = {

BACKGROUND: The successful prevention and treatment of coronary heart disease (CHD) and stroke has resulted in a substantial increase in longevity, with subsequent growth in the population of older people at risk for dementia.

OBJECTIVES: The authors evaluated the relationship of coronary and other peripheral atherosclerosis to risk of death, dementia, and CHD in the very elderly. Because the extent of vascular disease differs substantially between men and women, sex- and race-specific analyses were included, with a specific focus on women with low coronary artery calcium (CAC) Agatston scores.

METHODS: We evaluated the relationship between measures of subclinical cardiovascular disease (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) and risk of dementia, CHD, and total mortality in 532 participants of the Cardiovascular Health Study-Cognition Study from 1998/1999 (mean age, 80 years) to 2012/2013 (mean age, 93 years).

RESULTS: Thirty-six percent of participants had CAC scores >400. Women and African-Americans had lower CAC scores. Few men had low CAC scores. CAC score and number of coronary calcifications were directly related to age-adjusted total mortality and CHD. The age-specific incidence of dementia was higher than for CHD. Only about 25\% of deaths were caused by CHD and 16\% by dementia. Approximately 64\% of those who died had a prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia.

CONCLUSIONS: In subjects 80+ years of age, there is a greater incidence of dementia than of CHD. CAC, as a marker of atherosclerosis, is a determinant of mortality, and risk of CHD and myocardial infarction. White women with low CAC scores had a significantly decreased risk of dementia. A very important unanswered question, especially in the very elderly, is whether prevention of atherosclerosis and its complications is associated with less Alzheimer disease pathology and dementia. (Cardiovascular Health Study [CHS]; NCT00005133).

}, keywords = {Age Factors, Aged, 80 and over, Cause of Death, Coronary Artery Disease, Dementia, Female, Humans, Incidence, Male, Pennsylvania, Retrospective Studies, Risk Factors, Survival Rate}, issn = {1558-3597}, doi = {10.1016/j.jacc.2015.12.034}, author = {Kuller, Lewis H and Lopez, Oscar L and Mackey, Rachel H and Rosano, Caterina and Edmundowicz, Daniel and Becker, James T and Newman, Anne B} } @article {7777, title = {Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study.}, journal = {Hum Genet}, volume = {136}, year = {2017}, month = {2017 07}, pages = {897-902}, abstract = {

Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. We conducted a Mendelian Randomization study of body mass index (BMI) and VTE. We identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at P~<~0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95\% CI 1.02-1.12, P~=~0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR~=~1.59, 95\% CI 1.30-1.93 per standard deviation increase in BMI, P~=~5.8~{\texttimes}~10). Our study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE.

}, keywords = {Adult, Body Mass Index, Case-Control Studies, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Incidence, Logistic Models, Male, Mendelian Randomization Analysis, Obesity, Polymorphism, Single Nucleotide, Proportional Hazards Models, Venous Thromboembolism}, issn = {1432-1203}, doi = {10.1007/s00439-017-1811-x}, author = {Lindstr{\"o}m, Sara and Germain, Marine and Crous-Bou, Marta and Smith, Erin N and Morange, Pierre-Emmanuel and van Hylckama Vlieg, Astrid and de Haan, Hugoline G and Chasman, Daniel and Ridker, Paul and Brody, Jennifer and de Andrade, Mariza and Heit, John A and Tang, Weihong and DeVivo, Immaculata and Grodstein, Francine and Smith, Nicholas L and Tregouet, David and Kabrhel, Christopher} } @article {7547, title = {The Association Between IGF-I and IGFBP-3 and Incident Diabetes in an Older Population of Men and Women in the Cardiovascular Health Study.}, journal = {J Clin Endocrinol Metab}, volume = {102}, year = {2017}, month = {2017 Dec 01}, pages = {4541-4547}, abstract = {

Context: Insulin-like growth factor-I (IGF-I) has structural and functional similarities to insulin and may play a role in glucose homeostasis, along with insulin-like growth factor binding protein-3 (IGFBP-3), which binds the majority of circulating IGF-I.

Objective: To assess whether IGF-I and IGFBP-3 are associated with a higher risk of incident diabetes in older adults.

Design: Participants in the Cardiovascular Health Study (n = 3133), a cohort of adults aged >=65 years, were observed for 16 years (n = 3133) for the development of incident diabetes. Statistical models were fit separately for men and women because of interactions with sex (P interaction: IGF-I, 0.02; IGFBP-3, 0.009) and were adjusted for relevant covariates.

Setting: General community.

Participants: Older adults who were nondiabetic at baseline and who did not develop diabetes within the first year of follow-up.

Interventions: Not applicable.

Main Outcome Measure: Incident diabetes as measured by fasting plasma glucose (FPG) >=126 mg/dL, non-FPG >=200 mg/dL, use of pharmacological treatment of diabetes, or existence of two or more inpatient or three or more outpatient or (at least one inpatient and at least one outpatient) Centers for Medicare \& Medicaid Services claims with the diagnostic International Classification of Diseases, Ninth Revision, Clinical Modification code of 250.xx.

Results: In women, higher IGFBP-3 (hazard ratio tertile 3 vs tertile 1 = 2.30; 95\% confidence interval, 1.55 to 3.40; P trend < 0.0001) was significantly associated with incident diabetes. Total IGF-I was not significantly associated with incident diabetes. In men, neither IGF-I nor IGFBP-3 was significantly associated with incident diabetes.

Conclusions: We confirmed a previously reported association between circulating IGFBP-3 and diabetes risk in the older adult population, establishing that this association is present among women but could not be shown to be associated in men.

}, keywords = {Aged, Aged, 80 and over, Biomarkers, Blood Glucose, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Female, Humans, Incidence, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor I, Longitudinal Studies, Male, New England, Prospective Studies, Risk}, issn = {1945-7197}, doi = {10.1210/jc.2017-01273}, author = {Aneke-Nash, Chino S and Xue, XiaoNan and Qi, Qibin and Biggs, Mary L and Cappola, Anne and Kuller, Lewis and Pollak, Michael and Psaty, Bruce M and Siscovick, David and Mukamal, Kenneth and Strickler, Howard D and Kaplan, Robert C} } @article {7597, title = {Association of Diabetic Macular Edema and Proliferative Diabetic Retinopathy With Cardiovascular Disease: A Systematic Review and Meta-analysis.}, journal = {JAMA Ophthalmol}, volume = {135}, year = {2017}, month = {2017 Jun 01}, pages = {586-593}, abstract = {

Importance: Previous studies on the relationship between diabetic retinopathy (DR) and cardiovascular disease (CVD) focused on the early stages of DR. Understanding whether patients with type 2 diabetes and severe stages of DR (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]) have a higher risk of CVD will allow physicians to more effectively counsel patients.

Objective: To examine the association of severe stages of DR (DME and PDR) with incident CVD in patients with type 2 diabetes.

Data Sources: English-language publications were reviewed for articles evaluating the relationship of DR and CVD in MEDLINE, EMBASE, Current Contents, and the Cochrane Library from inception (January 1, 1950) to December 31, 2014, using the search terms diabetic retinopathy OR macular edema AND stroke OR cerebrovascular disease OR coronary artery disease OR heart failure OR myocardial infarction OR angina pectoris OR acute coronary syndrome OR coronary artery disease OR cardiomyopathy.

Study Selection: Among 656 studies screened for eligibility, 7604 individuals were included from 8 prospective population-based studies with data on photographic-based DR grading, follow-up visits, and well-defined incident CVD end point.

Data Extraction and Synthesis: Two independent reviewers conducted a systematic search of the 4 databases, and a single pooled database was developed. Incidence rate ratios (IRRs) were estimated for patients with DME, PDR, and vision-threatening DR, compared with persons without these conditions, by using individual participant data followed by a standard inverse-variance meta-analysis (2-step analysis). The review and analyses were performed from January 1, 2009, to January 1, 2017.

Main Outcome and Measures: Incident CVD, including coronary heart disease, stroke, or death from cardiovascular causes.

Results: Among 7604 patients with type 2 diabetes, the prevalence of DME was 4.6\% and PDR, 7.4\%. After a mean follow-up of 5.9 years (range, 3.2-10.1 years), 1203 incident CVD events, including 916 coronary heart disease cases, were reported. Persons with DME or PDR were more likely to have incident CVD (IRR, 1.39; 95\% CI, 1.16-1.67) and fatal CVD (IRR, 2.33; 95\% CI, 1.49-3.67) compared with those without DME or PDR.

Conclusions and Relevance: Patients with type 2 diabetes and DME or PDR have an increased risk of incident CVD, which suggests that these persons should be followed up more closely to prevent CVD.

}, keywords = {Cardiovascular Diseases, Diabetic Retinopathy, Global Health, Humans, Incidence, Macular Edema, Risk Factors}, issn = {2168-6173}, doi = {10.1001/jamaophthalmol.2017.0988}, author = {Xie, Jing and Ikram, M Kamran and Cotch, Mary Frances and Klein, Barbara and Varma, Rohit and Shaw, Jonathan E and Klein, Ronald and Mitchell, Paul and Lamoureux, Ecosse L and Wong, Tien Yin} } @article {7466, title = {Blood Pressure and Heart Rate Measures Associated With Increased Risk of Covert Brain Infarction and Worsening Leukoaraiosis in Older Adults.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {37}, year = {2017}, month = {2017 Aug}, pages = {1579-1586}, abstract = {

OBJECTIVE: In people without previous stroke, covert findings on serial magnetic resonance imaging (MRI) of incident brain infarcts and worsening leukoaraiosis are associated with increased risk for ischemic stroke and dementia. We evaluated whether various measures of blood pressure (BP) and heart rate are associated with these MRI findings.

APPROACH AND RESULTS: In the CHS (Cardiovascular Health Study), a longitudinal cohort study of older adults, we used relative risk regression to assess the associations of mean, variability, and trend in systolic BP, diastolic BP, and heart rate measured at 4 annual clinic visits between 2 brain MRIs with incident covert brain infarction and worsening white matter grade (using a 10-point scale to characterize leukoaraiosis). We included participants who had both brain MRIs, no stroke before the follow-up MRI, and no change in antihypertensive medication status during follow-up. Among 878 eligible participants, incident covert brain infarction occurred in 15\% and worsening white matter grade in 27\%. Mean systolic BP was associated with increased risk for incident covert brain infarction (relative risk per 10 mm Hg, 1.28; 95\% confidence interval, 1.12-1.47), and mean diastolic BP was associated with increased risk for worsening white matter grade (relative risk per 10 mm Hg, 1.45; 95\% confidence interval, 1.24-1.69). These findings persisted in secondary and sensitivity analyses.

CONCLUSIONS: Elevated mean systolic BP is associated with increased risk for covert brain infarction, and elevated mean diastolic BP is associated with increased risk for worsening leukoaraiosis. These findings reinforce the importance of hypertension in the development of silent cerebrovascular diseases, but the pathophysiologic relationships to BP for each may differ.

}, keywords = {Age Factors, Aged, Antihypertensive Agents, Blood Pressure, Cerebral Infarction, Disease Progression, Female, Heart Rate, Humans, Hypertension, Incidence, Leukoaraiosis, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prospective Studies, Pulsatile Flow, Risk Factors, Time Factors, United States}, issn = {1524-4636}, doi = {10.1161/ATVBAHA.117.309298}, author = {Leung, Lester Y and Bartz, Traci M and Rice, Kenneth and Floyd, James and Psaty, Bruce and Gutierrez, Jose and Longstreth, W T and Mukamal, Kenneth J} } @article {7563, title = {Concordance With Prevention Guidelines and Subsequent Cancer, Cardiovascular Disease, and Mortality: A Longitudinal Study of Older Adults.}, journal = {Am J Epidemiol}, volume = {186}, year = {2017}, month = {2017 Nov 15}, pages = {1168-1179}, abstract = {

Reports on the associations between multiple clinical and behavioral health indicators and major health outcomes among older adults are scarce. We prospectively examined concordance with guidelines from the American Cancer Society and American Heart Association for disease prevention in relation to cancer, cardiovascular disease (CVD), and mortality among Cardiovascular Health Study enrollees aged 65-98 years who, at baseline assessment in 1989-1996 (n = 3,491), were free of CVD and cancer. Total and cause-specific mortality, as well as incidence of cancer and CVD, were lower with higher guideline concordance. Independent of body mass index, blood pressure, total cholesterol, and fasting plasma glucose, better health behaviors (diet, physical activity, and alcohol consumption) were associated with lower mortality (2-sided P < 0.0001). Among individuals with ideal levels for 3-4 of these 4 cardiometabolic biomarkers, those with poor concordance with health behavior recommendations had higher mortality compared with those who had the highest concordance with these behavioral recommendations (adjusted mortality hazard ratio = 1.82, 95\% confidence interval: 1.25, 2.67). Older adults who are concordant with recommendations for cancer and CVD prevention have reduced rates of chronic disease and mortality. Interventions to achieve and maintain healthy lifestyle behaviors may offer benefits both in the presence and absence of adverse traditional clinical risk factors.

}, keywords = {Aged, Aged, 80 and over, American Cancer Society, American Heart Association, Body Mass Index, Cardiovascular Diseases, Cause of Death, Diet, Exercise, Female, Guideline Adherence, Healthy Lifestyle, Humans, Incidence, Longitudinal Studies, Male, Neoplasms, Practice Guidelines as Topic, Prospective Studies, United States}, issn = {1476-6256}, doi = {10.1093/aje/kwx150}, author = {Greenlee, Heather and Strizich, Garrett and Lovasi, Gina S and Kaplan, Robert C and Biggs, Mary L and Li, Christopher I and Richardson, John and Burke, Gregory L and Fitzpatrick, Annette L and Fretts, Amanda M and Psaty, Bruce M and Fried, Linda P} } @article {7490, title = {Omega-3 Fatty Acids and Incident Ischemic Stroke and Its Atherothrombotic and Cardioembolic Subtypes in 3 US Cohorts.}, journal = {Stroke}, volume = {48}, year = {2017}, month = {2017 Oct}, pages = {2678-2685}, abstract = {

BACKGROUND AND PURPOSE: The associations of individual long-chain n-3 polyunsaturated fatty acids with incident ischemic stroke and its main subtypes are not well established. We aimed to investigate prospectively the relationship of circulating eicosapentaenoic acid, docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with risk of total ischemic, atherothrombotic, and cardioembolic stroke.

METHODS: We measured circulating phospholipid fatty acids at baseline in 3 separate US cohorts: CHS (Cardiovascular Health Study), NHS (Nurses{\textquoteright} Health Study), and HPFS (Health Professionals Follow-Up Study). Ischemic strokes were prospectively adjudicated and classified into atherothrombotic (large- and small-vessel infarctions) or cardioembolic by imaging studies and medical records. Risk according to fatty acid levels was assessed using Cox proportional hazards (CHS) or conditional logistic regression (NHS, HPFS) according to study design. Cohort findings were pooled using fixed-effects meta-analysis.

RESULTS: A total of 953 incident ischemic strokes were identified (408 atherothrombotic, 256 cardioembolic, and 289 undetermined subtypes) during median follow-up of 11.2 years (CHS) and 8.3 years (pooled, NHS and HPFS). After multivariable adjustment, lower risk of total ischemic stroke was seen with higher DPA (highest versus lowest quartiles; pooled hazard ratio [HR], 0.74; 95\% confidence interval [CI], 0.58-0.92) and DHA (HR, 0.80; 95\% CI, 0.64-1.00) but not eicosapentaenoic acid (HR, 0.94; 95\% CI, 0.77-1.19). DHA was associated with lower risk of atherothrombotic stroke (HR, 0.53; 95\% CI, 0.34-0.83) and DPA with lower risk of cardioembolic stroke (HR, 0.58; 95\% CI, 0.37-0.92). Findings in each individual cohort were consistent with pooled results.

CONCLUSIONS: In 3 large US cohorts, higher circulating levels of DHA were inversely associated with incident atherothrombotic stroke and DPA with cardioembolic stroke. These novel findings suggest differential pathways of benefit for DHA, DPA, and eicosapentaenoic acid.

}, keywords = {Adult, Aged, Aged, 80 and over, Biomarkers, Brain Ischemia, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Fatty Acids, Omega-3, Female, Follow-Up Studies, Humans, Incidence, Intracranial Arteriosclerosis, Intracranial Embolism, Intracranial Thrombosis, Male, Middle Aged, Prospective Studies, Random Allocation, Risk Factors, Stroke, United States}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.117.018235}, author = {Saber, Hamidreza and Yakoob, Mohammad Yawar and Shi, Peilin and Longstreth, W T and Lemaitre, Rozenn N and Siscovick, David and Rexrode, Kathryn M and Willett, Walter C and Mozaffarian, Dariush} } @article {7550, title = {Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.}, journal = {Circulation}, volume = {136}, year = {2017}, month = {2017 Nov 28}, pages = {2100-2116}, abstract = {

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.

METHODS: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.

RESULTS: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5\%) had subclinical hypothyroidism and 2574 individuals (8.6\%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95\% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend <=0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.

CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

}, keywords = {Adult, Aged, Aged, 80 and over, Asymptomatic Diseases, Atrial Fibrillation, Biomarkers, Chi-Square Distribution, Female, Humans, Hypothyroidism, Incidence, Male, Middle Aged, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Risk Assessment, Risk Factors, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Time Factors, Young Adult}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.117.028753}, author = {Baumgartner, Christine and da Costa, Bruno R and Collet, Tinh-Hai and Feller, Martin and Floriani, Carmen and Bauer, Douglas C and Cappola, Anne R and Heckbert, Susan R and Ceresini, Graziano and Gussekloo, Jacobijn and den Elzen, Wendy P J and Peeters, Robin P and Luben, Robert and V{\"o}lzke, Henry and D{\"o}rr, Marcus and Walsh, John P and Bremner, Alexandra and Iacoviello, Massimo and Macfarlane, Peter and Heeringa, Jan and Stott, David J and Westendorp, Rudi G J and Khaw, Kay-Tee and Magnani, Jared W and Aujesky, Drahomir and Rodondi, Nicolas} } @article {8572, title = {Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study.}, journal = {Am J Hypertens}, volume = {30}, year = {2017}, month = {2017 Feb}, pages = {151-158}, abstract = {

BACKGROUND: Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability.

METHODS: We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual.

RESULTS: Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95\% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95\% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (>=10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95\% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95\% CI = 1.05-1.61); considerable increases of SBP (>=20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95\% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95\% CI = 1.08-1.74).

CONCLUSIONS: Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly.

}, keywords = {Aged, Aging, Blood Pressure, Blood Pressure Determination, Body Composition, California, Cohort Studies, Female, Health Status, Humans, Hypertension, Incidence, Longitudinal Studies, Male, Myocardial Infarction, Office Visits, Prognosis, Retrospective Studies, Risk Factors, Stroke, Survival Rate}, issn = {1941-7225}, doi = {10.1093/ajh/hpw106}, author = {Wu, Chenkai and Shlipak, Michael G and Stawski, Robert S and Peralta, Carmen A and Psaty, Bruce M and Harris, Tamara B and Satterfield, Suzanne and Shiroma, Eric J and Newman, Anne B and Odden, Michelle C} } @article {8041, title = {Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.}, journal = {PLoS Med}, volume = {15}, year = {2018}, month = {2018 10}, pages = {e1002670}, abstract = {

BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D).

METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95\% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist.

CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.

}, keywords = {Aged, Australia, Biomarkers, Dairy Products, Diabetes Mellitus, Type 2, Dietary Fats, Europe, Fatty Acids, Fatty Acids, Monounsaturated, Female, Humans, Incidence, Male, Middle Aged, Prospective Studies, Sex Factors, Taiwan, United States}, issn = {1549-1676}, doi = {10.1371/journal.pmed.1002670}, author = {Imamura, Fumiaki and Fretts, Amanda and Marklund, Matti and Ardisson Korat, Andres V and Yang, Wei-Sin and Lankinen, Maria and Qureshi, Waqas and Helmer, Catherine and Chen, Tzu-An and Wong, Kerry and Bassett, Julie K and Murphy, Rachel and Tintle, Nathan and Yu, Chaoyu Ian and Brouwer, Ingeborg A and Chien, Kuo-Liong and Frazier-Wood, Alexis C and Del Gobbo, Liana C and Djouss{\'e}, Luc and Geleijnse, Johanna M and Giles, Graham G and de Goede, Janette and Gudnason, Vilmundur and Harris, William S and Hodge, Allison and Hu, Frank and Koulman, Albert and Laakso, Markku and Lind, Lars and Lin, Hung-Ju and McKnight, Barbara and Rajaobelina, Kalina and Riserus, Ulf and Robinson, Jennifer G and Samieri, Cecilia and Siscovick, David S and Soedamah-Muthu, Sabita S and Sotoodehnia, Nona and Sun, Qi and Tsai, Michael Y and Uusitupa, Matti and Wagenknecht, Lynne E and Wareham, Nick J and Wu, Jason HY and Micha, Renata and Forouhi, Nita G and Lemaitre, Rozenn N and Mozaffarian, Dariush} } @article {8539, title = {Metabolic Clusters and Outcomes in Older Adults: The Cardiovascular Health Study.}, journal = {J Am Geriatr Soc}, volume = {66}, year = {2018}, month = {2018 02}, pages = {289-296}, abstract = {

BACKGROUND/OBJECTIVES: Few studies have the requisite phenotypic information to define metabolic patterns that may inform our understanding of the pathophysiology and consequences of diabetes in older adults. We sought to characterize clusters of older adults on the basis of shared metabolic features.

DESIGN: Population-based prospective cohort study.

SETTING: Four U.S. Cardiovascular Health Study field centers.

PARTICIPANTS: Individuals aged 65 and older taking no glucose-lowering agents (N~=~2,231).

MEASUREMENTS: K-means cluster analysis of 11 metabolic parameters (fasting and postload serum glucose and plasma insulin, fasting C-peptide, body mass index, C-reactive protein (CRP), estimated glomerular filtration rate (eGFR), albuminuria, carboxymethyl lysine (an advanced glycation end-product), procollagen III N-terminal propeptide (a fibrotic marker)) and their associations with incident cardiovascular disease, diabetes, disability, and mortality over 8 to 14.5~years of follow-up and with measures of subclinical cardiovascular disease.

RESULTS: A 6-cluster solution provided robust differentiation into distinct, identifiable clusters. Cluster A (n~=~739) had the lowest glucose and insulin and highest eGFR and the lowest rates of all outcomes. Cluster B (n~=~419) had high glucose and insulin and intermediate rates of most outcomes. Cluster C (n~=~118) had the highest insulin. Cluster D (n~=~129) had the highest glucose with much lower insulin. Cluster E (n~=~314) had the lowest eGFR and highest albuminuria. Cluster F (n~=~512) had the highest CRP. Rates of CVD, mortality, and subclinical atherosclerosis were highest in clusters C, D, and E and were similar to rates in participants with treated diabetes. Incidence of disability was highest in Cluster C.

CONCLUSION: Clustering according to metabolic parameters identifies distinct phenotypes that are strongly associated with clinical and functional outcomes, even at advanced age.

}, keywords = {Aged, Aged, 80 and over, Blood Glucose, C-Reactive Protein, Cardiovascular Diseases, Diabetes Mellitus, Female, Glomerular Filtration Rate, Humans, Incidence, Insulin, Longitudinal Studies, Male, Prospective Studies, Risk Factors, United States}, issn = {1532-5415}, doi = {10.1111/jgs.15205}, author = {Mukamal, Kenneth J and Siscovick, David S and de Boer, Ian H and Ix, Joachim H and Kizer, Jorge R and Djouss{\'e}, Luc and Fitzpatrick, Annette L and Tracy, Russell P and Boyko, Edward J and Kahn, Steven E and Arnold, Alice M} } @article {8507, title = {Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.}, journal = {Circulation}, volume = {140}, year = {2019}, month = {2019 08 20}, pages = {645-657}, abstract = {

BACKGROUND: DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts.

METHODS: Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts.

RESULTS: Among 11 461 individuals (mean age 64 years, 67\% women, 35\% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts.

CONCLUSION: Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.

}, keywords = {Adult, Aged, Cohort Studies, Coronary Disease, CpG Islands, DNA Methylation, Europe, Female, Genome-Wide Association Study, Humans, Incidence, Leukocytes, Male, Middle Aged, Myocardial Infarction, Population Groups, Prognosis, Prospective Studies, Risk, United States}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.118.039357}, author = {Agha, Golareh and Mendelson, Michael M and Ward-Caviness, Cavin K and Joehanes, Roby and Huan, Tianxiao and Gondalia, Rahul and Salfati, Elias and Brody, Jennifer A and Fiorito, Giovanni and Bressler, Jan and Chen, Brian H and Ligthart, Symen and Guarrera, Simonetta and Colicino, Elena and Just, Allan C and Wahl, Simone and Gieger, Christian and Vandiver, Amy R and Tanaka, Toshiko and Hernandez, Dena G and Pilling, Luke C and Singleton, Andrew B and Sacerdote, Carlotta and Krogh, Vittorio and Panico, Salvatore and Tumino, Rosario and Li, Yun and Zhang, Guosheng and Stewart, James D and Floyd, James S and Wiggins, Kerri L and Rotter, Jerome I and Multhaup, Michael and Bakulski, Kelly and Horvath, Steven and Tsao, Philip S and Absher, Devin M and Vokonas, Pantel and Hirschhorn, Joel and Fallin, M Daniele and Liu, Chunyu and Bandinelli, Stefania and Boerwinkle, Eric and Dehghan, Abbas and Schwartz, Joel D and Psaty, Bruce M and Feinberg, Andrew P and Hou, Lifang and Ferrucci, Luigi and Sotoodehnia, Nona and Matullo, Giuseppe and Peters, Annette and Fornage, Myriam and Assimes, Themistocles L and Whitsel, Eric A and Levy, Daniel and Baccarelli, Andrea A} } @article {8499, title = {Pre-diabetes, diabetes and predictors of incident angina among older women and men in the Cardiovascular Health Study.}, journal = {Diab Vasc Dis Res}, volume = {17}, year = {2020}, month = {2020 Jan-Feb}, pages = {1479164119888476}, abstract = {

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 {\textpm} 6.9 years of follow-up. Overall, 39.1\% of participants had pre-diabetes mellitus, 14.0\% had diabetes mellitus and 532 (11.8\%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all < 0.05 to < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris.

}, keywords = {Age Factors, Aged, Angina Pectoris, Diabetes Mellitus, Female, Humans, Incidence, Male, Prediabetic State, Prognosis, Prospective Studies, Risk Assessment, Risk Factors, Sex Factors, Time Factors, United States}, issn = {1752-8984}, doi = {10.1177/1479164119888476}, author = {Mathenge, Njambi and Fan, Wenjun and Wong, Nathan D and Hirsch, Calvin and Delaney, Chris Joseph and Amsterdam, Ezra A and Koch, Bruce and Calara, Rico and Gardin, Julius M} } @article {9001, title = {Epigenetic Age and the Risk of Incident Atrial Fibrillation.}, journal = {Circulation}, volume = {144}, year = {2021}, month = {2021 12 14}, pages = {1899-1911}, abstract = {

BACKGROUND: The most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF.

METHODS: Measures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF.

RESULTS: Among 5600 participants (mean age, 65.5 years; female, 60.1\%; Black, 50.7\%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19\% (adjusted hazard ratio [HR], 1.19 [95\% CI, 1.09-1.31]; <0.01) and 15\% (adjusted HR, 1.15 [95\% CI, 1.05-1.25]; <0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF.

CONCLUSIONS: Our study identified adjusted associations between EAA measures and incident AF, suggesting that biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.

}, keywords = {Aged, Aging, Atrial Fibrillation, DNA Methylation, Epigenesis, Genetic, Epigenomics, Female, Follow-Up Studies, Humans, Incidence, Male, Mendelian Randomization Analysis, Middle Aged, Models, Cardiovascular, Models, Genetic}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.121.056456}, author = {Roberts, Jason D and Vittinghoff, Eric and Lu, Ake T and Alonso, Alvaro and Wang, Biqi and Sitlani, Colleen M and Mohammadi-Shemirani, Pedrum and Fornage, Myriam and Kornej, Jelena and Brody, Jennifer A and Arking, Dan E and Lin, Honghuang and Heckbert, Susan R and Prokic, Ivana and Ghanbari, Mohsen and Skanes, Allan C and Bartz, Traci M and Perez, Marco V and Taylor, Kent D and Lubitz, Steven A and Ellinor, Patrick T and Lunetta, Kathryn L and Pankow, James S and Par{\'e}, Guillaume and Sotoodehnia, Nona and Benjamin, Emelia J and Horvath, Steve and Marcus, Gregory M} } @article {9090, title = {Monocyte subsets, T cell activation profiles, and stroke in men and women: The Multi-Ethnic Study of Atherosclerosis and Cardiovascular Health Study.}, journal = {Atherosclerosis}, volume = {351}, year = {2022}, month = {2022 06}, pages = {18-25}, abstract = {

BACKGROUND AND AIMS: Despite mechanistic data implicating unresolving inflammation in stroke pathogenesis, data regarding circulating immune cell phenotypes - key determinants of inflammation propagation versus resolution - and incident stroke are lacking. Therefore, we aimed to comprehensively define associations of circulating immune phenotypes and activation profiles with incident stroke.

METHODS: We investigated circulating leukocyte phenotypes and activation profiles with incident adjudicated stroke in 2104 diverse adults from the Multi-Ethnic Study of Atherosclerosis (MESA) followed over a median of 16.6 years. Cryopreserved cells from the MESA baseline examination were thawed and myeloid and lymphoid lineage cell subsets were measured using polychromatic flow cytometry and intracellular cytokine activation staining. We analyzed multivariable-adjusted associations of cell phenotypes, as a proportion of parent cell subsets, with incident stroke (overall) and ischemic stroke using Cox regression models.

RESULTS: We observed associations of intermediate monocytes, early-activated CD4 T cells, and both CD4 and CD8 T cells producing interleukin-4 after cytokine stimulation (T and T, respectively) with higher risk for incident stroke; effect sizes ranged from 35\% to 62\% relative increases in risk for stroke. Meanwhile, differentiated and memory T cell phenotypes were associated with lower risk for incident stroke. In sex-stratified analyses, positive and negative associations were especially strong among men but null among women.

CONCLUSIONS: Circulating IL-4 producing T cells and intermediate monocytes were significantly associated with incident stroke over nearly two decades of follow-up. These associations were stronger among men and not among women. Further translational studies are warranted to define more precise targets for prognosis and intervention.

}, keywords = {Atherosclerosis, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, Female, Follow-Up Studies, Humans, Incidence, Inflammation, Interleukin-4, Ischemic Stroke, Lymphocyte Activation, Male, Monocytes, Stroke, T-Lymphocyte Subsets}, issn = {1879-1484}, doi = {10.1016/j.atherosclerosis.2022.05.007}, author = {Feinstein, Matthew J and B{\r u}zkov{\'a}, Petra and Olson, Nels C and Doyle, Margaret F and Sitlani, Colleen M and Fohner, Alison E and Huber, Sally A and Floyd, James and Sinha, Arjun and Thorp, Edward B and Landay, Alan and Freiberg, Matthew S and Longstreth, William T and Tracy, Russell P and Psaty, Bruce M and Delaney, Joseph Ac} } @article {9486, title = {Association between 5-year change in cardiovascular risk and the incidence of atherosclerotic cardiovascular diseases: a multi-cohort study.}, journal = {J Transl Med}, volume = {21}, year = {2023}, month = {2023 Sep 02}, pages = {589}, abstract = {

BACKGROUND: The influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence.

METHODS: We analyzed pooled data from seven community-based prospective cohort studies with up to 20~years of follow-up data. The study populations included White or Black participants aged 40-75~years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20\%) or high risk (>= 20\%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD.

RESULTS: Among 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7\%) were female and 3127 (28.4\%) were Black. During a median follow-up period of 9.9~years, 2560 (23.2\%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95\% confidence interval [CI] 0.59-0.77) or high to non-high (HR, 0.57; 95\% CI 0.41-0.80) and those with a consistently non-high risk (HR, 0.33; 95\% CI 0.29-0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95\% CI 1.26-2.41) or from non-high to high risk (HR, 2.04; 95\% CI 1.84-2.27) and those with a consistently high risk (HR 3.03; 95\% CI 2.69-3.42) also showed an increased risk of incident ASCVD.

CONCLUSIONS: Individuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account.

}, keywords = {Atherosclerosis, Cardiovascular Diseases, Cohort Studies, Female, Heart Disease Risk Factors, Humans, Incidence, Male, Middle Aged, Prospective Studies, Risk Factors}, issn = {1479-5876}, doi = {10.1186/s12967-023-04488-7}, author = {Yi, Jiayi and Wang, Lili and Guo, Xinli and Ren, Xiangpeng} } @article {9448, title = {CHARGE-AF: A Useful Score For Atrial Fibrillation Prediction?}, journal = {Curr Cardiol Rev}, volume = {19}, year = {2023}, month = {2023}, pages = {e010922208402}, abstract = {

Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased morbidity and mortality. Various predictive scores for new-onset AF have been proposed, but so far, none have been widely used in clinical practice. CHARGE-AF score was developed from a pooled diverse population from three large cohorts (Atherosclerosis Risk in Communities study, Cardiovascular Health Study and Framingham Heart Study). A simple 5-year predictive model includes the variables of age, race, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes mellitus, history of myocardial infarction and heart failure. Recent studies report that the CHARGE-AF score has good discrimination for incident AF and seems to be a promising prediction model for this arrhythmia. New screening tools (smartphone apps, smartwatches) are rapidly developing for AF detection. Therefore, the wide application of the CHARGE-AF score in clinical practice and the upcoming usage of mobile health technologies and smartwatches may result in better AF prediction and adequate stroke prevention, especially in high-risk patients.

}, keywords = {Atherosclerosis, Atrial Fibrillation, Heart Failure, Humans, Incidence, Myocardial Infarction, Risk Assessment, Risk Factors}, issn = {1875-6557}, doi = {10.2174/1573403X18666220901102557}, author = {Goudis, Christos and Daios, Stylianos and Dimitriadis, Fotios and Liu, Tong} } @article {9485, title = {Elevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS.}, journal = {J Am Heart Assoc}, volume = {12}, year = {2023}, month = {2023 Sep 05}, pages = {e029960}, abstract = {

Background Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50\% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95\% CI, 1.0-1.9]; =0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95\% CI, 1.0-1.3]; =0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95\% CI, 1.1-2.7]; =0.01). Conclusions Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.

}, keywords = {Aged, Aging, Cardiovascular Diseases, Heart Failure, Humans, Incidence, Ketone Bodies}, issn = {2047-9980}, doi = {10.1161/JAHA.123.029960}, author = {Niezen, Sebastian and Connelly, Margery A and Hirsch, Calvin and Kizer, Jorge R and Benitez, Maria E and Minchenberg, Scott and Perez-Matos, Maria Camila and Jiang, Zhenghui Gordon and Mukamal, Kenneth J} }